{"id":5177,"date":"2024-01-16T12:37:46","date_gmt":"2024-01-16T12:37:46","guid":{"rendered":"https:\/\/farlong.com\/?p=5177"},"modified":"2024-01-27T10:26:20","modified_gmt":"2024-01-27T10:26:20","slug":"breviscapine-remodels-myocardial-glucose-and-lipid-metabolism-by-regulating-serotonin-to-alleviate-doxorubicin-induced-cardiotoxicity","status":"publish","type":"post","link":"https:\/\/directcm.com\/vi\/breviscapine-remodels-myocardial-glucose-and-lipid-metabolism-by-regulating-serotonin-to-alleviate-doxorubicin-induced-cardiotoxicity\/","title":{"rendered":"Breviscapine \u0111i\u1ec1u ch\u1ec9nh qu\u00e1 tr\u00ecnh chuy\u1ec3n h\u00f3a glucose v\u00e0 lipid c\u1ee7a c\u01a1 tim b\u1eb1ng c\u00e1ch \u0111i\u1ec1u ch\u1ec9nh serotonin \u0111\u1ec3 l\u00e0m gi\u1ea3m \u0111\u1ed9c t\u00ednh tr\u00ean tim do doxorubicin g\u00e2y ra"},"content":{"rendered":"

Meng-Jiao Li, 1 , 2 , \u2020 Wen-She Sun, 1 , \u2020 Yang Yuan, 1 , \u2020 Yu-Kun Zhang, 1 , 2 Qi Lu, 1 , 2 Yuan-Zhen Gao, 1 , 2 Ting Ye, 1 , 2 v\u00e0 Dong-Ming Xingt\u00e1c gi\u1ea3 t\u01b0\u01a1ng \u1ee9ng 1 , 3 ,*<\/p>\n

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tr\u1eebu t\u01b0\u1ee3ng<\/h2>\n
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M\u1ee5c ti\u00eau:<\/strong>\u00a0Thu\u1ed1c ch\u1ed1ng ung th\u01b0 ph\u1ed5 r\u1ed9ng doxorubicin (Dox) c\u00f3 li\u00ean quan \u0111\u1ebfn t\u1ef7 l\u1ec7 nhi\u1ec5m \u0111\u1ed9c tim cao, \u1ea3nh h\u01b0\u1edfng nghi\u00eam tr\u1ecdng \u0111\u1ebfn \u1ee9ng d\u1ee5ng l\u00e2m s\u00e0ng c\u1ee7a thu\u1ed1c v\u00e0 ch\u1ea5t l\u01b0\u1ee3ng cu\u1ed9c s\u1ed1ng c\u1ee7a b\u1ec7nh nh\u00e2n. \u1ede \u0111\u00e2y, ch\u00fang t\u00f4i \u0111\u00e1nh gi\u00e1 c\u00e1ch Dox \u0111i\u1ec1u ch\u1ec9nh n\u0103ng l\u01b0\u1ee3ng v\u00e0 ch\u1ee9c n\u0103ng co b\u00f3p c\u1ee7a c\u01a1 tim v\u00e0 \u0111i\u1ec1u n\u00e0y c\u00f3 th\u1ec3 h\u1ed7 tr\u1ee3 ph\u00e1t tri\u1ec3n c\u00e1c lo\u1ea1i thu\u1ed1c b\u1ea3o v\u1ec7 c\u00f3 li\u00ean quan.<\/p>\n

Ph\u01b0\u01a1ng ph\u00e1p:<\/strong>\u00a0Chu\u1ed9t \u0111\u00e3 \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng doxorubicin v\u00e0 breviscapine. Ch\u1ee9c n\u0103ng tim \u0111\u01b0\u1ee3c ph\u00e2n t\u00edch b\u1eb1ng si\u00eau \u00e2m tim v\u00e0 t\u00edn hi\u1ec7u qua trung gian Dox \u0111\u01b0\u1ee3c \u0111\u00e1nh gi\u00e1 trong c\u00e1c t\u1ebf b\u00e0o c\u01a1 tim bi\u1ec7t l\u1eadp. T\u00e1c d\u1ee5ng k\u00e9p b\u1ea3o v\u1ec7 tim m\u1ea1ch v\u00e0 ch\u1ed1ng kh\u1ed1i u c\u1ee7a breviscapine \u0111\u00e3 \u0111\u01b0\u1ee3c \u0111\u00e1nh gi\u00e1 tr\u00ean m\u00f4 h\u00ecnh kh\u1ed1i u v\u00fa \u1edf chu\u1ed9t.<\/p>\n

K\u1ebft qu\u1ea3:<\/strong>\u00a0Ch\u00fang t\u00f4i th\u1ea5y r\u1eb1ng Dox ph\u00e1 v\u1ee1 qu\u00e1 tr\u00ecnh chuy\u1ec3n h\u00f3a n\u0103ng l\u01b0\u1ee3ng c\u1ee7a c\u01a1 tim b\u1eb1ng c\u00e1ch gi\u1ea3m s\u1ef1 h\u1ea5p thu glucose v\u00e0 t\u0103ng qu\u00e1 tr\u00ecnh oxy h\u00f3a axit b\u00e9o, d\u1eabn \u0111\u1ebfn gi\u1ea3m t\u1ed1c \u0111\u1ed9 s\u1ea3n xu\u1ea5t ATP, t\u0103ng t\u1ed1c \u0111\u1ed9 ti\u00eau th\u1ee5 oxy v\u00e0 stress oxy h\u00f3a, \u0111\u1ed3ng th\u1eddi thi\u1ebfu h\u1ee5t n\u0103ng l\u01b0\u1ee3ng h\u01a1n n\u1eefa \u0111\u1ec3 t\u0103ng c\u01b0\u1eddng h\u1ea5p thu axit b\u00e9o c\u1ee7a c\u01a1 tim v\u00e0 th\u00fac \u0111\u1ea9y DIC ph\u00e1t tri\u1ec3n. \u0110i\u1ec1u th\u00fa v\u1ecb l\u00e0, breviscapine l\u00e0m t\u0103ng hi\u1ec7u qu\u1ea3 s\u1ea3n xu\u1ea5t ATP v\u00e0 ph\u1ee5c h\u1ed3i c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i n\u0103ng l\u01b0\u1ee3ng c\u1ee7a c\u01a1 tim b\u1eb1ng c\u00e1ch \u0111i\u1ec1u ch\u1ec9nh v\u00f2ng PI3K\/AKT c\u01a1 tim serotonin-glucose, t\u0103ng c\u01b0\u1eddng s\u1eed d\u1ee5ng glucose \u1edf tim v\u00e0 gi\u1ea3m qu\u00e1 tr\u00ecnh oxy h\u00f3a lipid. N\u00f3 t\u0103ng c\u01b0\u1eddng kh\u1ea3 n\u0103ng t\u1ef1 th\u1ef1c c\u1ee7a ty th\u1ec3\u00a0th\u00f4ng qua<\/em>\u00a0con \u0111\u01b0\u1eddng PINK1\/Parkin, lo\u1ea1i b\u1ecf s\u1ef1 t\u00edch t\u1ee5 ty th\u1ec3 b\u1ecb t\u1ed5n th\u01b0\u01a1ng do Dox g\u00e2y ra, l\u00e0m gi\u1ea3m m\u1ee9c \u0111\u1ed9 x\u01a1 h\u00f3a v\u00e0 vi\u00eam tim, \u0111\u1ed3ng th\u1eddi ph\u1ee5c h\u1ed3i c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i vi m\u00f4 c\u1ee7a tim. \u0110i\u1ec1u quan tr\u1ecdng l\u00e0 m\u1ee9c \u0111\u1ed9 vi\u00eam th\u1ea5p c\u1ee7a n\u00f3 l\u00e0m gi\u1ea3m s\u1ef1 x\u00e2m nh\u1eadp c\u1ee7a t\u1ebf b\u00e0o \u1ee9c ch\u1ebf mi\u1ec5n d\u1ecbch d\u00f2ng t\u1ee7y v\u00e0 t\u00e1c d\u1ee5ng n\u00e0y c\u00f3 t\u00e1c d\u1ee5ng hi\u1ec7p \u0111\u1ed3ng v\u1edbi t\u00e1c d\u1ee5ng ch\u1ed1ng kh\u1ed1i u c\u1ee7a Dox.<\/p>\n

Ph\u1ea7n k\u1ebft lu\u1eadn:<\/strong>\u00a0Nh\u1eefng ph\u00e1t hi\u1ec7n c\u1ee7a ch\u00fang t\u00f4i cho th\u1ea5y r\u1eb1ng s\u1ef1 gi\u00e1n \u0111o\u1ea1n m\u1ea1ng l\u01b0\u1edbi trao \u0111\u1ed5i ch\u1ea5t c\u1ee7a tim do Dox l\u00e0 nguy\u00ean nh\u00e2n quan tr\u1ecdng g\u00e2y ra \u0111\u1ed9c t\u00ednh tr\u00ean tim v\u00e0 serotonin l\u00e0 ch\u1ea5t \u0111i\u1ec1u ch\u1ec9nh quan tr\u1ecdng qu\u00e1 tr\u00ecnh chuy\u1ec3n h\u00f3a glucose v\u00e0 lipid c\u1ee7a c\u01a1 tim. C\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i n\u0103ng l\u01b0\u1ee3ng c\u01a1 tim v\u00e0 gi\u1ea3i ph\u00f3ng k\u1ecbp th\u1eddi c\u00e1c ty th\u1ec3 b\u1ecb t\u1ed5n th\u01b0\u01a1ng g\u00f3p ph\u1ea7n hi\u1ec7p \u0111\u1ed3ng v\u00e0o vi\u1ec7c ng\u0103n ng\u1eeba nhi\u1ec5m \u0111\u1ed9c tim do anthracycline g\u00e2y ra v\u00e0 n\u00e2ng cao hi\u1ec7u qu\u1ea3 \u0111i\u1ec1u tr\u1ecb kh\u1ed1i u.<\/p>\n<\/div>\n

T\u1eeb kh\u00f3a:\u00a0<\/strong>doxorubicin, DIC, breviscapine, serotonin, PINK1\/Parkin<\/span><\/div>\n<\/div>\n
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\u0110i \u0111\u1ebfn:<\/a><\/div>\n

Gi\u1edbi thi\u1ec7u<\/h2>\n

Thu\u1ed1c kh\u00e1ng sinh anthracycline doxorubicin (Dox) l\u00e0 m\u1ed9t ch\u1ea5t ch\u1ed1ng ung th\u01b0 hi\u1ec7u qu\u1ea3 cao \u0111\u1ec3 \u0111i\u1ec1u tr\u1ecb c\u00e1c kh\u1ed1i u r\u1eafn, b\u1ec7nh b\u1ea1ch c\u1ea7u, u lympho v\u00e0 ung th\u01b0 v\u00fa.Takemura v\u00e0 Fujiwara, 2007<\/a>). Vi\u1ec7c s\u1eed d\u1ee5ng Dox c\u00f3 th\u1ec3 d\u1eabn \u0111\u1ebfn b\u1ec7nh c\u01a1 tim ti\u1ebfn tri\u1ec3n, m\u00e3n t\u00ednh, \u0111e d\u1ecda t\u00ednh m\u1ea1ng \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 b\u1ec7nh c\u01a1 tim do Dox (DIC) (Levis v\u00e0 c\u1ed9ng s\u1ef1, 2017<\/a>;\u00a0Sawicki v\u00e0 c\u1ed9ng s\u1ef1, 2021<\/a>). \u0110\u00e1ng ch\u00fa \u00fd, \u1edf b\u1ec7nh nh\u00e2n ung th\u01b0, nguy c\u01a1 t\u1eed vong do nhi\u1ec5m \u0111\u1ed9c tim li\u00ean quan \u0111\u1ebfn thu\u1ed1c cao h\u01a1n nguy c\u01a1 t\u1eed vong do ch\u00ednh kh\u1ed1i u ho\u1eb7c nguy c\u01a1 t\u00e1i ph\u00e1t (L\u01b0u v\u00e0 c\u1ed9ng s\u1ef1, 2017<\/a>). DIC do nhi\u1ec5m \u0111\u1ed9c tim c\u00f3 th\u1ec3 x\u1ea3y ra sau khi d\u00f9ng Dox li\u1ec1u th\u1ea5p t\u00f9y thu\u1ed9c v\u00e0o \u0111\u1ed9 nh\u1ea1y c\u1ea3m c\u1ee7a t\u1eebng c\u00e1 nh\u00e2n (McGowan v\u00e0 c\u1ed9ng s\u1ef1, 2017<\/a>). C\u00e1c nghi\u00ean c\u1ee9u d\u1ecbch t\u1ec5 h\u1ecdc \u0111\u00e3 ch\u1ec9 ra r\u1eb1ng c\u00e1c b\u1ea5t th\u01b0\u1eddng v\u1ec1 chuy\u1ec3n h\u00f3a, ch\u1eb3ng h\u1ea1n nh\u01b0 b\u00e9o ph\u00ec, ti\u1ec3u \u0111\u01b0\u1eddng v\u00e0 b\u1ec7nh gan, d\u1eabn \u0111\u1ebfn t\u0103ng nguy c\u01a1 m\u1eafc DIC v\u00e0 Dox l\u00e0m gi\u1ea3m m\u1ea1nh s\u1ef1 h\u1ea5p thu glucose c\u1ee7a tim, cho th\u1ea5y Dox c\u00f3 th\u1ec3 \u1ea3nh h\u01b0\u1edfng \u0111\u1ebfn s\u1ef1 ph\u00e1t tri\u1ec3n c\u1ee7a DIC b\u1eb1ng c\u00e1ch ph\u00e1 v\u1ee1 qu\u00e1 tr\u00ecnh m\u00f4i tr\u01b0\u1eddng vi m\u00f4 trao \u0111\u1ed5i ch\u1ea5t c\u1ee7a tim. G\u1ea7n \u0111\u00e2y, c\u00e1c nghi\u00ean c\u1ee9u v\u1ec1 c\u01a1 ch\u1ebf ph\u00e2n t\u1eed ti\u1ec1m n\u0103ng c\u1ee7a DIC \u0111\u00e3 t\u1eadp trung v\u00e0o s\u1ef1 m\u1ea5t c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i c\u1ee7a b\u00f2 \u0111\u1ecf, \u1ee9c ch\u1ebf phi\u00ean m\u00e3 topoisomerase II\u03b2 (Top2b), r\u1ed1i lo\u1ea1n ch\u1ee9c n\u0103ng ty th\u1ec3 v\u00e0 Ca2+<\/sup>- X\u1eed l\u00fd c\u00e1c b\u1ea5t th\u01b0\u1eddng (Vejpongsa v\u00e0 Yeh, 2014<\/a>;\u00a0Kalyanaraman, 2020<\/a>;\u00a0Hulst v\u00e0 c\u1ed9ng s\u1ef1, 2021<\/a>). Tr\u00e1i tim ti\u00eau th\u1ee5 l\u01b0\u1ee3ng n\u0103ng l\u01b0\u1ee3ng l\u1edbn nh\u1ea5t trong c\u01a1 th\u1ec3 v\u00e0 Dox \u0111\u1ecbnh h\u00ecnh l\u1ea1i qu\u00e1 tr\u00ecnh trao \u0111\u1ed5i ch\u1ea5t c\u1ee7a tim. Tuy nhi\u00ean, nh\u1eefng thay \u0111\u1ed5i th\u00fac \u0111\u1ea9y s\u1ef1 ph\u00e1t tri\u1ec3n c\u1ee7a DIC v\u1eabn ch\u01b0a \u0111\u01b0\u1ee3c hi\u1ec3u \u0111\u1ea7y \u0111\u1ee7. C\u00e1c chi\u1ebfn l\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb \u0111\u1ec3 ng\u0103n ng\u1eeba DIC th\u00f4ng qua vi\u1ec7c \u0111i\u1ec1u h\u00f2a m\u1ea1ng l\u01b0\u1edbi chuy\u1ec3n h\u00f3a c\u1ee7a tim ch\u01b0a \u0111\u01b0\u1ee3c thi\u1ebft l\u1eadp.<\/p>\n

Chuy\u1ec3n h\u00f3a n\u0103ng l\u01b0\u1ee3ng c\u1ee7a tim bao g\u1ed3m c\u00e1c t\u1eadp h\u1ee3p ph\u1ee9c t\u1ea1p c\u1ee7a c\u00e1c con \u0111\u01b0\u1eddng t\u01b0\u01a1ng t\u00e1c d\u1eabn \u0111\u1ebfn vi\u1ec7c s\u1eed d\u1ee5ng c\u01a1 ch\u1ea5t n\u0103ng l\u01b0\u1ee3ng c\u1ee7a t\u1eebng lo\u1ea1i \u0111\u1ec3 s\u1ea3n xu\u1ea5t ho\u1eb7c sinh t\u1ed5ng h\u1ee3p ATP. \u0110\u1eb7c \u0111i\u1ec3m n\u1ed5i b\u1eadt nh\u1ea5t c\u1ee7a m\u1ea1ng l\u01b0\u1edbi l\u00e0 t\u00ednh linh ho\u1ea1t trao \u0111\u1ed5i ch\u1ea5t \u0111\u01b0\u1ee3c th\u1ec3 hi\u1ec7n \u0111\u1ec3 \u0111\u00e1p \u1ee9ng v\u1edbi c\u00e1c k\u00edch th\u00edch kh\u00e1c nhau, bao g\u1ed3m nh\u1eefng thay \u0111\u1ed5i v\u1ec1 ph\u00e1t tri\u1ec3n, t\u00ecnh tr\u1ea1ng dinh d\u01b0\u1ee1ng, t\u00ecnh tr\u1ea1ng sinh l\u00fd b\u1ec7nh m\u00e3n t\u00ednh v\u00e0 c\u00e1c can thi\u1ec7p d\u01b0\u1ee3c l\u00fd (Murashige v\u00e0 c\u1ed9ng s\u1ef1, 2020<\/a>). Ty th\u1ec3, l\u00e0 c\u00e1c b\u00e0o quan \u0111a n\u0103ng chi\u1ebfm 1\/3 th\u1ec3 t\u00edch t\u1ebf b\u00e0o c\u01a1 tim v\u00e0 kh\u00f4ng ch\u1ec9 t\u1ea1o ra h\u01a1n 95% ATP \u0111\u01b0\u1ee3c tim s\u1eed d\u1ee5ng m\u00e0 c\u00f2n \u0111i\u1ec1u h\u00f2a c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i canxi n\u1ed9i b\u00e0o, truy\u1ec1n t\u00edn hi\u1ec7u v\u00e0 ch\u1ebft t\u1ebf b\u00e0o, l\u00e0 trung t\u00e2m c\u1ee7a n\u0103ng l\u01b0\u1ee3ng ph\u1ed1i h\u1ee3p s\u1ef1 truy\u1ec1n t\u1ea3i (Kolwicz v\u00e0 c\u1ed9ng s\u1ef1, 2013<\/a>). M\u1eb7c d\u00f9 tim c\u00f3 kh\u1ea3 n\u0103ng s\u1eed d\u1ee5ng t\u1ea5t c\u1ea3 c\u00e1c lo\u1ea1i ch\u1ea5t n\u1ec1n n\u0103ng l\u01b0\u1ee3ng, bao g\u1ed3m carbohydrate, lipid, axit amin v\u00e0 th\u1ec3 ketone \u0111\u1ec3 s\u1ea3n xu\u1ea5t ATP, ch\u1ea5t n\u1ec1n \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng s\u1ebd \u1ea3nh h\u01b0\u1edfng \u0111\u1ebfn hi\u1ec7u qu\u1ea3 c\u1ee7a tim. N\u1ed3ng \u0111\u1ed9 axit b\u00e9o v\u00e0 qu\u00e1 tr\u00ecnh oxy h\u00f3a t\u0103ng cao c\u00f3 li\u00ean quan \u0111\u1ebfn vi\u1ec7c gi\u1ea3m qu\u00e1 tr\u00ecnh oxy h\u00f3a glucose trong b\u1ed1i c\u1ea3nh b\u00e9o ph\u00ec v\u00e0 ti\u1ec3u \u0111\u01b0\u1eddng (Randle v\u00e0 c\u1ed9ng s\u1ef1, 1963<\/a>;\u00a0L\u00fd v\u00e0 Tr\u01b0\u01a1ng, 2016<\/a>). R\u1ed1i lo\u1ea1n ch\u1ee9c n\u0103ng tim c\u00f3 li\u00ean quan \u0111\u1ebfn vi\u1ec7c t\u0103ng ti\u00eau th\u1ee5 oxy c\u1ee7a c\u01a1 tim, gi\u1ea3m hi\u1ec7u qu\u1ea3 c\u1ee7a tim v\u00e0 t\u0103ng c\u0103ng th\u1eb3ng oxy h\u00f3a, cho th\u1ea5y r\u1eb1ng qu\u00e1 tr\u00ecnh oxy h\u00f3a axit b\u00e9o t\u0103ng l\u00ean (FAO) c\u00f3 h\u1ea1i cho ch\u1ee9c n\u0103ng tim (Lopaschuk v\u00e0 c\u1ed9ng s\u1ef1, 2010<\/a>;\u00a0Lopaschuk v\u00e0 c\u1ed9ng s\u1ef1, 2021<\/a>;\u00a0Yamamoto v\u00e0 Sano, 2022<\/a>). M\u1ed9t c\u01a1 ch\u1ebf g\u00e2y ra t\u00e1c d\u1ee5ng ph\u1ee5 c\u1ee7a FAO cao l\u00e0 l\u00e0m gi\u1ea3m hi\u1ec7u qu\u1ea3 s\u1eed d\u1ee5ng oxy v\u00e0 t\u0103ng m\u1ee9c \u0111\u1ed9 d\u1eabn xu\u1ea5t axit b\u00e9o, \u0111i\u1ec1u n\u00e0y c\u00f3 th\u1ec3 l\u00e0m gi\u1ea3m hi\u1ec7u qu\u1ea3 h\u01a1n n\u1eefa do t\u00e1ch ty th\u1ec3. Tr\u00ean th\u1ef1c t\u1ebf, s\u1ef1 gia t\u0103ng peroxid h\u00f3a lipid (LP) \u0111\u01b0\u1ee3c quan s\u00e1t th\u1ea5y \u1edf DIC, cho th\u1ea5y FAO cao c\u00f3 th\u1ec3 l\u00e0 con \u0111\u01b0\u1eddng ch\u00ednh d\u1eabn \u0111\u1ebfn t\u1ed5n th\u01b0\u01a1ng tim. Do \u0111\u00f3, ch\u00fang t\u00f4i \u0111\u01b0a ra gi\u1ea3 thuy\u1ebft r\u1eb1ng qu\u00e1 tr\u00ecnh t\u00e1i c\u1ea5u tr\u00fac trao \u0111\u1ed5i ch\u1ea5t c\u1ee7a tim trong qu\u00e1 tr\u00ecnh \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox l\u00e0m t\u0103ng s\u1ef1 h\u1ea5p thu v\u00e0 oxy h\u00f3a axit b\u00e9o, d\u1eabn \u0111\u1ebfn hi\u1ec7u qu\u1ea3 s\u1ea3n xu\u1ea5t ATP th\u1ea5p, k\u00e8m theo m\u1ee9c ti\u00eau th\u1ee5 oxy cao v\u00e0 stress oxy h\u00f3a, \u0111\u1ed3ng th\u1eddi l\u00e0m gi\u1ea3m hi\u1ec7u qu\u1ea3 c\u1ee7a tim, t\u1eeb \u0111\u00f3 l\u00e0m gi\u1ea3m hi\u1ec7u qu\u1ea3 s\u1eed d\u1ee5ng axit b\u00e9o. v\u00e0 t\u1ed5n th\u01b0\u01a1ng ty th\u1ec3, t\u1eeb \u0111\u00f3 \u0111\u1ea9y nhanh s\u1ef1 ti\u1ebfn tri\u1ec3n c\u1ee7a DIC.<\/p>\n

\u0110i\u1ec1u th\u00fa v\u1ecb l\u00e0 c\u00e1c nghi\u00ean c\u1ee9u d\u1ecbch t\u1ec5 h\u1ecdc cho th\u1ea5y r\u1eb1ng vi\u1ec7c ti\u00eau th\u1ee5 th\u01b0\u1eddng xuy\u00ean th\u1ef1c ph\u1ea9m gi\u00e0u flavonoid c\u00f3 th\u1ec3 l\u00e0m gi\u1ea3m nguy c\u01a1 m\u1eafc nhi\u1ec1u b\u1ec7nh tim m\u1ea1ch v\u00e0 nhi\u1ec1u h\u1ee3p ch\u1ea5t flavonoid t\u1ef1 nhi\u00ean \u0111\u00e3 \u0111\u01b0\u1ee3c ch\u1ee9ng minh l\u00e0 c\u00f3 t\u00e1c d\u1ee5ng b\u1ea3o v\u1ec7 ch\u1ee9c n\u0103ng tim (Shabalala v\u00e0 c\u1ed9ng s\u1ef1, 2017<\/a>;\u00a0Syahputra v\u00e0 c\u1ed9ng s\u1ef1, 2022<\/a>).\u00a0Erigeron breviscapus<\/em>, c\u00f2n \u0111\u01b0\u1ee3c bi\u1ebft l\u00e0\u00a0Asherpa breviscapine<\/em>\u00a0hay Apocynum, l\u00e0 m\u1ed9t lo\u1ea1i th\u1ea3o m\u1ed9c truy\u1ec1n th\u1ed1ng \u0111\u00e3 \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng h\u01a1n 600 n\u0103m. Breviscapine l\u00e0 th\u00e0nh ph\u1ea7n flavonoid c\u1ee7a\u00a0Erigeron breviscapus<\/em>\u00a0c\u00f3 nhi\u1ec1u t\u00e1c d\u1ee5ng d\u01b0\u1ee3c l\u00fd, ch\u1eb3ng h\u1ea1n nh\u01b0 t\u00e1c d\u1ee5ng ch\u1ed1ng oxy h\u00f3a, ch\u1ed1ng vi\u00eam v\u00e0 ch\u1ed1ng ung th\u01b0 (Gao v\u00e0 c\u1ed9ng s\u1ef1, 2017<\/a>;\u00a0Wen v\u00e0 c\u1ed9ng s\u1ef1, 2021<\/a>). Thu\u1ed1c ti\u00eam Breviscapine l\u00e0 lo\u1ea1i thu\u1ed1c c\u1ed5 \u0111i\u1ec3n \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng r\u1ed9ng r\u00e3i nh\u1ea5t \u0111\u1ec3 \u0111i\u1ec1u tr\u1ecb c\u00e1c b\u1ec7nh tim m\u1ea1ch v\u00e0 m\u1ea1ch m\u00e1u n\u00e3o \u1edf Trung Qu\u1ed1c, \u0111\u1ed3ng th\u1eddi n\u00f3 c\u0169ng l\u00e0 m\u1ed9t lo\u1ea1i thu\u1ed1c quan tr\u1ecdng \u0111\u1ec3 \u0111i\u1ec1u tr\u1ecb c\u1ea5p c\u1ee9u t\u1ea1i c\u00e1c b\u1ec7nh vi\u1ec7n Trung Qu\u1ed1c. Breviscapine \u0111\u00e3 \u0111\u01b0\u1ee3c \u00e1p d\u1ee5ng l\u00e2m s\u00e0ng \u0111\u1ec3 \u0111i\u1ec1u tr\u1ecb t\u0103ng huy\u1ebft \u00e1p, t\u1eafc m\u1ea1ch n\u00e3o v\u00e0 c\u00e1c b\u1ec7nh m\u1ea1ch m\u00e1u n\u00e3o trong h\u01a1n 20 n\u0103m (Wu v\u00e0 c\u1ed9ng s\u1ef1, 2019<\/a>). Tuy nhi\u00ean, hi\u1ec7n t\u1ea1i kh\u00f4ng c\u00f3 b\u00e1o c\u00e1o n\u00e0o v\u1ec1 t\u00e1c d\u1ee5ng b\u1ea3o v\u1ec7 c\u1ee7a n\u00f3 \u0111\u1ed1i v\u1edbi t\u1ed5n th\u01b0\u01a1ng tim do thu\u1ed1c h\u00f3a tr\u1ecb g\u00e2y ra.<\/p>\n

Trong nghi\u00ean c\u1ee9u n\u00e0y, ch\u00fang t\u00f4i \u0111\u00e3 kh\u00e1m ph\u00e1 nh\u1eefng t\u00e1c \u0111\u1ed9ng ti\u1ec1m t\u00e0ng c\u1ee7a breviscapine \u0111\u1ed1i v\u1edbi DIC v\u00e0 c\u00e1c c\u01a1 ch\u1ebf ph\u00e2n t\u1eed c\u00f3 th\u1ec3 c\u00f3 c\u1ee7a n\u00f3 b\u1eb1ng c\u00e1ch thi\u1ebft l\u1eadp m\u00f4 h\u00ecnh t\u1ed5n th\u01b0\u01a1ng c\u01a1 tim do anthracycline g\u00e2y ra b\u1eb1ng c\u00e1ch s\u1eed d\u1ee5ng t\u1ebf b\u00e0o c\u01a1 tim chu\u1ed9t H9c2 v\u00e0 chu\u1ed9t C57BL\/6. Ch\u00fang t\u00f4i c\u0169ng \u0111\u00e3 l\u00e0m s\u00e1ng t\u1ecf m\u1ed9t c\u00e1ch c\u00f3 h\u1ec7 th\u1ed1ng r\u1eb1ng breviscapine c\u00f3 th\u1ec3 c\u1ea3i thi\u1ec7n hi\u1ec7u qu\u1ea3 s\u1eed d\u1ee5ng glucose c\u1ee7a c\u01a1 tim th\u00f4ng qua con \u0111\u01b0\u1eddng serotonin ph\u00e2n nh\u00e1nh \u0111\u01b0\u1ee3c \u0111i\u1ec1u ch\u1ec9nh b\u1eb1ng glucose, do \u0111\u00f3 ph\u00e1t huy c\u00e1c ch\u1ee9c n\u0103ng gi\u1ed1ng nh\u01b0 insulin \u0111\u1ec3 \u0111\u1ea1t \u0111\u01b0\u1ee3c hi\u1ec7u qu\u1ea3 s\u1ea3n xu\u1ea5t ATP cao v\u00e0 m\u1ee9c \u0111\u1ed9 c\u0103ng th\u1eb3ng oxy h\u00f3a th\u1ea5p trong khi ti\u00eau th\u1ee5 oxy th\u1ea5p h\u01a1n v\u00e0 n\u00f3 c\u00f3 th\u1ec3 k\u00edch ho\u1ea1t c\u01a1 ch\u1ebf c\u1ed5 \u0111i\u1ec3n. Con \u0111\u01b0\u1eddng t\u1ef1 th\u1ef1c b\u00e0o PINK1\/Parkin c\u1ee7a ty th\u1ec3 \u0111\u1ec3 lo\u1ea1i b\u1ecf s\u1ef1 t\u00edch t\u1ee5 dox g\u00e2y ra c\u1ee7a ty th\u1ec3 b\u1ecb t\u1ed5n th\u01b0\u01a1ng, ph\u1ed1i h\u1ee3p \u0111i\u1ec1u h\u00f2a stress oxy h\u00f3a v\u00e0 s\u1ea3n xu\u1ea5t n\u0103ng l\u01b0\u1ee3ng, v\u00e0 d\u1ea7n d\u1ea7n kh\u00f4i ph\u1ee5c c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i c\u1ee7a vi m\u00f4i tr\u01b0\u1eddng tim. Ng\u01b0\u1eddi ta cho r\u1eb1ng breviscapine l\u00e0 m\u1ed9t ch\u1ea5t b\u1ea3o v\u1ec7 m\u1edbi ti\u1ec1m n\u0103ng \u0111\u1ed1i v\u1edbi \u0111\u1ed9c t\u00ednh tr\u00ean tim do doxorubicin g\u00e2y ra.<\/p>\n<\/div>\n

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\u0110i \u0111\u1ebfn:<\/a><\/div>\n

Nguy\u00ean li\u1ec7u v\u00e0 ph\u01b0\u01a1ng ph\u00e1p<\/h2>\n

T\u1ea5t c\u1ea3 c\u00e1c nghi\u00ean c\u1ee9u tr\u00ean \u0111\u1ed9ng v\u1eadt \u0111\u00e3 \u0111\u01b0\u1ee3c ph\u00ea duy\u1ec7t v\u00e0 th\u1ef1c hi\u1ec7n theo h\u01b0\u1edbng d\u1eabn c\u1ee7a \u1ee6y ban Ch\u0103m s\u00f3c v\u00e0 S\u1eed d\u1ee5ng \u0110\u1ed9ng v\u1eadt \u0110\u1ea1i h\u1ecdc Thanh \u0110\u1ea3o.<\/p>\n

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Thu\u1ed1c th\u1eed<\/h3>\n

C\u00e1c thu\u1ed1c th\u1eed sau \u0111\u00e3 \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng: DMEM, FBS, penicillin\/streptomycin (Meilunbio, \u0110\u1ea1i Li\u00ean, Trung Qu\u1ed1c), b\u1ed9 d\u1ee5ng c\u1ee5 cTnI Elisa (Sangon Biotech, Th\u01b0\u1ee3ng H\u1ea3i, Trung Qu\u1ed1c), b\u1ed9 d\u1ee5ng c\u1ee5 TNF-\u03b1, IL-1\u03b2 v\u00e0 IL-6 Elisa (MyBioSource, San Diego, Hoa K\u1ef3), b\u1ed9 d\u1ee5ng c\u1ee5 MDA, b\u1ed9 d\u1ee5ng c\u1ee5 SOD v\u00e0 b\u1ed9 d\u1ee5ng c\u1ee5 NADH (Solarbio, B\u1eafc Kinh, Trung Qu\u1ed1c), b\u1ed9 d\u1ee5ng c\u1ee5 CCK-8 (C\u00f4ng ngh\u1ec7 sinh h\u1ecdc Beyotime, Th\u01b0\u1ee3ng H\u1ea3i, Trung Qu\u1ed1c), b\u1ed9 d\u1ee5ng c\u1ee5 \u0111o hu\u1ef3nh quang ROS, thu\u1ed1c nhu\u1ed9m hu\u1ef3nh quang JC-1, b\u1ed9 d\u1ee5ng c\u1ee5 chi\u1ebft protein v\u00e0 b\u1ed9 d\u1ee5ng c\u1ee5 BCA (Meilunbio, \u0110\u1ea1i Li\u00ean, Trung Qu\u1ed1c). IL-1 (1:100), PINK1(1:1.000), Parkin (1:1.000), AMPK(1:1.000), Akt (1:1.000), P13K(1:1.000), Tom20 (1:1.000) , \u03b2-tubulin (1:1.000), mTOR (1:1.000) v\u00e0 kh\u00e1ng th\u1ec3 GAPDH (1:1.000) li\u00ean h\u1ee3p HRP \u0111\u01b0\u1ee3c l\u1ea5y t\u1eeb C\u00f4ng ngh\u1ec7 sinh h\u1ecdc Abclonal (V\u0169 H\u00e1n, Trung Qu\u1ed1c). B\u1ed9 \u0111\u1ec7m ly gi\u1ea3i v\u00e0 b\u1ed9 \u0111\u1ec7m t\u1ea3i RIPA \u0111\u01b0\u1ee3c mua t\u1eeb Meilunbio (\u0110\u1ea1i Li\u00ean, Trung Qu\u1ed1c). M\u00e0ng PVDF \u0111\u01b0\u1ee3c l\u1ea5y t\u1eeb Merck (New Jersey, Hoa K\u1ef3). DMSO \u0111\u01b0\u1ee3c mua t\u1eeb Macklin (Th\u01b0\u1ee3ng H\u1ea3i, Trung Qu\u1ed1c) v\u00e0 doxorubicin, breviscapine v\u00e0 dexrazoxane \u0111\u01b0\u1ee3c mua t\u1eeb Widely (V\u0169 H\u00e1n, Trung Qu\u1ed1c). Ch\u1ea5t \u1ee9c ch\u1ebf Mdivi-1 \u0111\u01b0\u1ee3c mua t\u1eeb Selleck Chemicals (Houston, Hoa K\u1ef3).<\/p>\n<\/div>\n

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\u0110i\u1ec1u ki\u1ec7n nu\u00f4i c\u1ea5y t\u1ebf b\u00e0o v\u00e0 d\u00f2ng t\u1ebf b\u00e0o<\/h3>\n

M\u00f4i tr\u01b0\u1eddng nu\u00f4i c\u1ea5y v\u00e0 ch\u1ea5t b\u1ed5 sung cho nu\u00f4i c\u1ea5y t\u1ebf b\u00e0o \u0111\u01b0\u1ee3c mua t\u1eeb Gibco-Invitrogen (Carlsbad, CA, Hoa K\u1ef3) v\u00e0 \u0111\u1ed3 nh\u1ef1a \u0111\u01b0\u1ee3c mua t\u1eeb Corning (Corning, NY, Hoa K\u1ef3). C\u00e1c t\u1ebf b\u00e0o nguy\u00ean b\u00e0o c\u01a1 tim c\u00f3 ngu\u1ed3n g\u1ed1c t\u1eeb tim ph\u00f4i chu\u1ed9t H9c2 (ATCC, CRL-1446) \u0111\u01b0\u1ee3c nu\u00f4i c\u1ea5y trong DMEM ch\u1ee9a 10% huy\u1ebft thanh b\u00f2 b\u00e0o thai, natri penicillin G 100 \u0111\u01a1n v\u1ecb\/ml v\u00e0 streptomycin sulfate 100 \u03bcg\/ml (37\u00b0C, 5% CO2<\/sub>). C\u00e1c t\u1ebf b\u00e0o ung th\u01b0 v\u00fa di c\u0103n MCF-7 \u1edf ng\u01b0\u1eddi (iCell, iCell-h129) \u0111\u01b0\u1ee3c nu\u00f4i c\u1ea5y trong 1.640 m\u00f4i tr\u01b0\u1eddng b\u1ed5 sung huy\u1ebft thanh b\u00e0o thai b\u00f2 10%, natri penicillin G 100 \u0111\u01a1n v\u1ecb\/ml v\u00e0 streptomycin sulfat 100 \u03bcg\/ml. T\u1ebf b\u00e0o ung th\u01b0 v\u00fa chu\u1ed9t 4T1 (ATCC, FS-0158) \u0111\u01b0\u1ee3c nu\u00f4i c\u1ea5y trong m\u00f4i tr\u01b0\u1eddng DMEM b\u1ed5 sung huy\u1ebft thanh b\u00e0o thai b\u00f2 10%, natri penicillin G 100 \u0111\u01a1n v\u1ecb\/ml v\u00e0 streptomycin sulfate 100 \u03bcg\/ml.<\/p>\n

C\u00e1c t\u1ebf b\u00e0o \u0111\u01b0\u1ee3c di chuy\u1ec3n th\u01b0\u1eddng xuy\u00ean khi ch\u00fang \u0111\u1ea1t \u0111\u1ebfn \u0111i\u1ec3m h\u1ee3p l\u01b0u 80\u201390% v\u00e0 \u0111\u01b0\u1ee3c gieo v\u00e0o c\u00e1c \u0111\u0129a 96 gi\u1ebfng (1 \u00d7 104<\/sup>\u00a0t\u1ebf b\u00e0o\/gi\u1ebfng). C\u00e1c t\u1ebf b\u00e0o H9c2 \u0111\u01b0\u1ee3c ti\u1ebfp x\u00fac v\u1edbi \u0111i\u1ec1u khi\u1ec3n, 5 \u03bcM Dox (Guo v\u00e0 c\u1ed9ng s\u1ef1, 2013<\/a>), 5 \u03bcM Dox+20 \u03bcM Dexra (Sangweni v\u00e0 c\u1ed9ng s\u1ef1, 2020<\/a>) ho\u1eb7c 5 \u03bcM Dox+200 \u03bcM breviscapine (Li v\u00e0 c\u1ed9ng s\u1ef1, 2022<\/a>) t\u01b0\u01a1ng \u1ee9ng trong 24 gi\u1edd. C\u00e1c t\u1ebf b\u00e0o \u0111\u01b0\u1ee3c x\u1eed l\u00fd b\u1eb1ng DMEM ch\u1ec9 \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng l\u00e0m \u0111\u1ed1i ch\u1ee9ng tr\u1ed1ng v\u00e0 Dexra \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng l\u00e0m \u0111\u1ed1i ch\u1ee9ng d\u01b0\u01a1ng. Cu\u1ed1i c\u00f9ng, ch\u00fang t\u00f4i c\u0169ng ti\u00eam Mdivi-1 (5\u03bcM, trong DMSO), m\u1ed9t ch\u1ea5t \u1ee9c ch\u1ebf s\u1ef1 ph\u00e2n chia ty th\u1ec3 (Nh\u01b0 v\u00e0 c\u1ed9ng s\u1ef1, 2021<\/a>).<\/p>\n<\/div>\n

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\u0110\u00e1nh gi\u00e1 stress oxy h\u00f3a<\/h3>\n

N\u1ed3ng \u0111\u1ed9 ROS n\u1ed9i b\u00e0o \u0111\u01b0\u1ee3c \u0111o b\u1eb1ng thu\u1ed1c nhu\u1ed9m hu\u1ef3nh quang DCFH-DA theo h\u01b0\u1edbng d\u1eabn c\u1ee7a nh\u00e0 s\u1ea3n xu\u1ea5t. T\u00f3m l\u1ea1i, dung d\u1ecbch DCFH-DA (1 \u03bcM) \u0111\u01b0\u1ee3c chu\u1ea9n b\u1ecb trong PBS v\u00e0 \u0111\u01b0\u1ee3c th\u00eam v\u00e0o c\u00e1c t\u1ebf b\u00e0o H9c2 \u0111\u01b0\u1ee3c nu\u00f4i c\u1ea5y trong \u0111\u0129a 6 gi\u1ebfng tr\u01b0\u1edbc khi \u1ee7 \u1edf 37\u00b0C trong 30 ph\u00fat. Sau khi \u1ee7, t\u1ebf b\u00e0o \u0111\u01b0\u1ee3c r\u1eeda b\u1eb1ng PBS. M\u00e1y ch\u1ee5p \u1ea3nh quang h\u1ecdc hu\u1ef3nh quang \u0111\u01b0\u1ee3c ch\u1ee5p \u1edf \u0111\u1ed9 ph\u00f3ng \u0111\u1ea1i 20 \u00d7 b\u1eb1ng k\u00ednh hi\u1ec3n vi hu\u1ef3nh quang t\u1eeb Leica Microsystems, Ltd. N\u1ed3ng \u0111\u1ed9 ROS \u0111\u01b0\u1ee3c \u0111\u1ecbnh l\u01b0\u1ee3ng b\u1eb1ng m\u00e1y \u0111o d\u00f2ng ch\u1ea3y Beckman (Beckman, California, Hoa K\u1ef3).<\/p>\n<\/div>\n

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X\u00e1c \u0111\u1ecbnh ch\u1ec9 s\u1ed1 enzym<\/h3>\n

Ho\u1ea1t t\u00ednh c\u1ee7a SOD v\u00e0 NADH \u0111\u01b0\u1ee3c \u0111o b\u1eb1ng b\u1ed9 x\u00e9t nghi\u1ec7m ho\u1ea1t t\u00ednh theo h\u01b0\u1edbng d\u1eabn c\u1ee7a nh\u00e0 s\u1ea3n xu\u1ea5t. \u0110\u1ed9 h\u1ea5p th\u1ee5 v\u00e0 \u0111\u1ed9 ph\u00e1t quang \u0111\u01b0\u1ee3c \u0111o b\u1eb1ng m\u00e1y \u0111\u1ecdc vi b\u1ea3n (Perkin Elmer, Massachusetts, Hoa K\u1ef3).<\/p>\n<\/div>\n

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K\u00ednh hi\u1ec3n vi \u0111i\u1ec7n t\u1eed<\/h3>\n

C\u00e1c t\u1ebf b\u00e0o \u0111\u01b0\u1ee3c c\u1ed1 \u0111\u1ecbnh b\u1eb1ng ch\u1ea5t c\u1ed1 \u0111\u1ecbnh glutaraldehyde 0,5% \u1edf 4\u00b0C trong 15\u201330 ph\u00fat v\u00e0 \u0111\u01b0\u1ee3c thu th\u1eadp b\u1eb1ng c\u00e1ch ly t\u00e2m \u1edf t\u1ed1c \u0111\u1ed9 10.000\u201313.000 v\u00f2ng\/ph\u00fat trong 5 ph\u00fat. C\u00e1c t\u1ebf b\u00e0o \u0111\u01b0\u1ee3c c\u1ed1 \u0111\u1ecbnh th\u00eam b\u1eb1ng 3% glutaraldehyde \u1edf 4\u00b0C qua \u0111\u00eam v\u00e0 sau \u0111\u00f3 \u0111\u01b0\u1ee3c x\u1eed l\u00fd b\u1eb1ng 1% osmium tetroxide \u1edf nhi\u1ec7t \u0111\u1ed9 ph\u00f2ng trong 2 gi\u1edd. Sau \u0111\u00f3, c\u00e1c m\u1eabu \u0111\u01b0\u1ee3c kh\u1eed n\u01b0\u1edbc trong gradient axeton, \u0111\u01b0\u1ee3c nh\u00fang v\u00e0o Epon 812, \u0111\u01b0\u1ee3c \u0111\u1ecbnh v\u1ecb quang h\u1ecdc v\u00e0 c\u1eaft th\u00e0nh c\u00e1c ph\u1ea7n si\u00eau m\u1ecfng. C\u00e1c ph\u1ea7n \u0111\u01b0\u1ee3c nhu\u1ed9m hai l\u1ea7n b\u1eb1ng uranyl acetate v\u00e0 ch\u00ec citrate. C\u01a1 s\u1edf h\u1ea1 t\u1ea7ng c\u1ee7a ty th\u1ec3 \u0111\u01b0\u1ee3c ki\u1ec3m tra b\u1eb1ng k\u00ednh hi\u1ec3n vi \u0111i\u1ec7n t\u1eed truy\u1ec1n qua H-7650 (Hitachi, Toyko, Nh\u1eadt B\u1ea3n).<\/p>\n<\/div>\n

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X\u00e1c \u0111\u1ecbnh h\u00f4 h\u1ea5p c\u1ee7a ty th\u1ec3<\/h3>\n

Kho\u1ea3ng 106<\/sup>\u00a0c\u00e1c t\u1ebf b\u00e0o \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng \u0111\u1ec3 \u0111o h\u00f4 h\u1ea5p c\u1ee7a ty th\u1ec3 b\u1eb1ng m\u00e1y \u0111o h\u00f4 h\u1ea5p O2K (D\u1ee5ng c\u1ee5 Oroboros, \u00c1o). N\u1ed3ng \u0111\u1ed9 oxy \u0111\u01b0\u1ee3c x\u00e1c \u0111\u1ecbnh v\u00e0 ph\u00e2n t\u00edch b\u1eb1ng ph\u1ea7n m\u1ec1m Oroboros DatLab 7.4. T\u00f3m l\u1ea1i, tr\u1ea1ng th\u00e1i h\u00f4 h\u1ea5p r\u00f2 r\u1ec9 \u0111\u00e3 \u0111\u01b0\u1ee3c ghi l\u1ea1i ch\u1ec9 trong c\u00e1c t\u1ebf b\u00e0o, s\u1ef1 chuy\u1ec3n \u0111i\u1ec7n t\u1eed \u0111\u01b0\u1ee3c k\u1ebft h\u1ee3p v\u1edbi qu\u00e1 tr\u00ecnh phosphoryl h\u00f3a b\u1eb1ng c\u00e1ch b\u1ed5 sung 5 mM ADP v\u00e0 h\u00f4 h\u1ea5p tr\u1ea1ng th\u00e1i 3 \u0111\u01b0\u1ee3c h\u1ed7 tr\u1ee3 b\u1edfi ph\u1ee9c h\u1ee3p I \u0111\u00e3 \u0111\u01b0\u1ee3c ghi l\u1ea1i. H\u00f4 h\u1ea5p \u1edf tr\u1ea1ng th\u00e1i t\u1ed1i \u0111a 3 v\u1edbi \u0111\u1ea7u v\u00e0o electron song song t\u1eeb ph\u1ee9c I v\u00e0 ph\u1ee9c II \u0111\u01b0\u1ee3c ghi l\u1ea1i th\u00f4ng qua vi\u1ec7c b\u1ed5 sung 10 mM succinate v\u00e0 h\u00f4 h\u1ea5p ph\u1ee9c h\u1ee3p II \u0111\u01b0\u1ee3c h\u1ed7 tr\u1ee3 \u0111\u01b0\u1ee3c \u0111o v\u1edbi s\u1ef1 c\u00f3 m\u1eb7t c\u1ee7a 6,25 \u00b5M rotenone. Kh\u1ea3 n\u0103ng truy\u1ec1n \u0111i\u1ec7n t\u1eed t\u1ed1i \u0111a \u0111\u01b0\u1ee3c ghi nh\u1eadn khi c\u00f3 m\u1eb7t 5 \u00b5M cacbonyl xyanua p-(trifluoro-methoxy) phenyl-hydrazone (FCCP). Cu\u1ed1i c\u00f9ng, antimycin (Ama), ch\u1ea5t ho\u00e0n th\u00e0nh ph\u1ee9c h\u1ee3p \u2162 v\u00e0 ng\u0103n ch\u1eb7n t\u1ea5t c\u1ea3 s\u1ef1 v\u1eadn chuy\u1ec3n \u0111i\u1ec7n t\u1eed, \u0111\u00e3 \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng v\u00e0 t\u1ed1c \u0111\u1ed9 ti\u00eau th\u1ee5 oxy \u0111\u01b0\u1ee3c \u0111o b\u1eb1ng m\u1ee9c ti\u00eau th\u1ee5 oxy kh\u00f4ng ph\u1ea3i c\u1ee7a ty th\u1ec3.<\/p>\n<\/div>\n

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X\u00e1c \u0111\u1ecbnh s\u1ef1 thay \u0111\u1ed5i \u0111i\u1ec7n th\u1ebf m\u00e0ng ty th\u1ec3 (\u0394\u03a8m)<\/h3>\n

Nhu\u1ed9m 5,5\u2032,6,6\u2032-Tetrachloro-1,1\u2032,3,3\u2032-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng \u0111\u1ec3 \u0111\u00e1nh gi\u00e1 ti\u1ec1m n\u0103ng m\u00e0ng ty th\u1ec3 trong t\u1ebf b\u00e0o H9c2. T\u00f3m l\u1ea1i, theo c\u00e1c \u0111i\u1ec1u ki\u1ec7n th\u00ed nghi\u1ec7m \u0111\u00e3 x\u00e1c \u0111\u1ecbnh tr\u01b0\u1edbc, t\u1ebf b\u00e0o H9c2 \u0111\u01b0\u1ee3c r\u1eeda b\u1eb1ng dung d\u1ecbch mu\u1ed1i \u0111\u1ec7m ph\u1ed1t ph\u00e1t (DPBS) \u1ea5m c\u1ee7a Dulbecco tr\u01b0\u1edbc khi nhu\u1ed9m b\u1eb1ng 100 \u03bcL dung d\u1ecbch 2 \u03bcM JC-1 (tr\u1ed9n trong DMEM kh\u00f4ng c\u00f3 m\u00e0u \u0111\u1ecf phenol) v\u00e0 \u1ee7 trong m\u00f4i tr\u01b0\u1eddng nu\u00f4i c\u1ea5y t\u1ebf b\u00e0o ti\u00eau chu\u1ea9n. \u0111i\u1ec1u ki\u1ec7n trong b\u00f3ng t\u1ed1i 30 ph\u00fat. Sau khi \u1ee7, c\u00e1c t\u1ebf b\u00e0o \u0111\u01b0\u1ee3c r\u1eeda b\u1eb1ng DPBS \u1ea5m v\u00e0 ch\u1ee5p \u1ea3nh vi m\u00f4 hu\u1ef3nh quang \u0111\u01b0\u1ee3c ch\u1ee5p \u1edf \u0111\u1ed9 ph\u00f3ng \u0111\u1ea1i 20 l\u1ea7n b\u1eb1ng k\u00ednh hi\u1ec3n vi hu\u1ef3nh quang \u0111\u1ea3o ng\u01b0\u1ee3c Leica Microsystems CMS GmbH (Leica Camera AG, Barnack, German).<\/p>\n<\/div>\n

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Mi\u1ec5n d\u1ecbch hu\u1ef3nh quang<\/h3>\n

\u0110\u1ec3 \u0111\u00e1nh gi\u00e1 qu\u00e1 tr\u00ecnh \u0111\u1ecbnh v\u1ecb ty th\u1ec3, c\u00e1c t\u1ebf b\u00e0o ph\u00e1t tri\u1ec3n tr\u00ean n\u1eafp \u0111\u1eady \u0111\u01b0\u1ee3c r\u1eeda b\u1eb1ng PBS l\u1ea1nh v\u00e0 c\u1ed1 \u0111\u1ecbnh b\u1eb1ng paraformaldehyde 4% trong 15 ph\u00fat. Sau \u0111\u00f3, c\u00e1c t\u1ebf b\u00e0o \u0111\u01b0\u1ee3c th\u1ea9m th\u1ea5u b\u1eb1ng 0,5% Triton X-100 trong 20 ph\u00fat v\u00e0 phong b\u1ebf b\u1eb1ng huy\u1ebft thanh d\u00ea 5% trong 30 ph\u00fat. C\u00e1c t\u1ebf b\u00e0o \u0111\u01b0\u1ee3c \u1ee7 v\u1edbi kh\u00e1ng th\u1ec3 s\u01a1 c\u1ea5p qua \u0111\u00eam \u1edf 4\u00b0C v\u00e0 v\u1edbi kh\u00e1ng th\u1ec3 th\u1ee9 c\u1ea5p trong 1 gi\u1edd. Sau khi r\u1eeda ba l\u1ea7n, c\u00e1c t\u1ebf b\u00e0o \u0111\u01b0\u1ee3c nhu\u1ed9m b\u1eb1ng 4\u2032-6-diamidino-2-phenylindole (DAPI) v\u00e0 ch\u1ee5p \u1ea3nh b\u1eb1ng k\u00ednh hi\u1ec3n vi qu\u00e9t laser \u0111\u1ed3ng ti\u00eau.<\/p>\n<\/div>\n

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\u0110o ATP<\/h3>\n

Ngo\u00e0i ra, n\u1ed3ng \u0111\u1ed9 ATP n\u1ed9i b\u00e0o \u0111\u01b0\u1ee3c \u0111o b\u1eb1ng c\u00e1ch s\u1eed d\u1ee5ng b\u1ed9 x\u00e9t nghi\u1ec7m ATP theo quy tr\u00ecnh c\u1ee7a nh\u00e0 s\u1ea3n xu\u1ea5t. C\u00e1c t\u1ebf b\u00e0o \u0111\u01b0\u1ee3c ly gi\u1ea3i trong dung d\u1ecbch \u0111\u1ec7m ly gi\u1ea3i b\u1eb1ng c\u00e1ch l\u1eb7p l\u1ea1i thao t\u00e1c pipet v\u00e0 ly t\u00e2m \u1edf 4\u00b0C v\u00e0 13.000 g trong 10 ph\u00fat. Ch\u1ea5t n\u1ed5i ph\u00eda tr\u00ean \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng \u0111\u1ec3 ph\u00e2n t\u00edch n\u1ed3ng \u0111\u1ed9 ATP v\u00e0 n\u1ed3ng \u0111\u1ed9 protein \u0111\u01b0\u1ee3c x\u00e1c \u0111\u1ecbnh b\u1eb1ng x\u00e9t nghi\u1ec7m BCA. M\u1ed9t th\u1ec3 t\u00edch 50 microlit ch\u1ea5t n\u1ed5i ph\u00eda tr\u00ean \u0111\u01b0\u1ee3c th\u00eam v\u00e0o 100 \u03bcl dung d\u1ecbch ph\u00e1t hi\u1ec7n ATP, \u1ee7 \u1edf nhi\u1ec7t \u0111\u1ed9 ph\u00f2ng trong 5 ph\u00fat v\u00e0 tr\u1ed9n ngay l\u1eadp t\u1ee9c, \u0111\u1ed3ng th\u1eddi \u0111\u1ed9 ph\u00e1t quang \u0111\u01b0\u1ee3c x\u00e1c \u0111\u1ecbnh b\u1eb1ng m\u00e1y \u0111o \u0111\u1ed9 s\u00e1ng (Flex Station 3). N\u1ed3ng \u0111\u1ed9 ATP \u0111\u01b0\u1ee3c t\u00ednh to\u00e1n theo \u0111\u01b0\u1eddng chu\u1ea9n v\u00e0 chuy\u1ec3n \u0111\u1ed5i th\u00e0nh protein nmol\/\u03bcg.<\/p>\n<\/div>\n

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Ph\u01b0\u01a1ng T\u00e2y th\u1ea5m<\/h3>\n

Bi\u1ec3u hi\u1ec7n protein \u0111\u01b0\u1ee3c \u0111\u00e1nh gi\u00e1 b\u1eb1ng ph\u01b0\u01a1ng ph\u00e1p Western blot v\u00e0 \u0111\u1ecbnh l\u01b0\u1ee3ng b\u1eb1ng ph\u00e9p \u0111o m\u1eadt \u0111\u1ed9. C\u00e1c t\u1ebf b\u00e0o H9c2 \u0111\u01b0\u1ee3c x\u1eed l\u00fd b\u1eb1ng Dox v\u00e0 Dox + Brev trong c\u00e1c \u0111\u0129a nu\u00f4i c\u1ea5y t\u1ebf b\u00e0o 10 cm \u0111\u01b0\u1ee3c l\u1ecdc b\u1eb1ng dung d\u1ecbch \u0111\u1ec7m ly gi\u1ea3i RIPA. L\u1ea5y 5 mg m\u00f4 v\u00e0 th\u00eam 10 ml dung d\u1ecbch \u0111\u1ec7m ly gi\u1ea3i. Ph\u01b0\u01a1ng ph\u00e1p Bradford \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng \u0111\u1ec3 \u0111o n\u1ed3ng \u0111\u1ed9 protein, s\u1eed d\u1ee5ng BSA l\u00e0m ti\u00eau chu\u1ea9n. L\u01b0\u1ee3ng protein t\u01b0\u01a1ng \u0111\u01b0\u01a1ng \u0111\u01b0\u1ee3c tr\u1ed9n v\u1edbi dung d\u1ecbch \u0111\u1ec7m t\u1ea3i (5X) v\u00e0 \u0111un s\u00f4i \u1edf 95\u00b0C trong 5 ph\u00fat. Sau \u0111\u00f3, c\u00e1c protein \u0111\u01b0\u1ee3c ph\u00e2n gi\u1ea3i b\u1eb1ng \u0111i\u1ec7n di tr\u00ean gel 10%\u201312% SDS-polyacrylamide (TRANG SDS) v\u00e0 chuy\u1ec3n v\u00e0o m\u00e0ng PVDF. Sau khi ng\u0103n ch\u1eb7n b\u1eb1ng s\u1eefa 5% trong TBST trong 2 gi\u1edd \u1edf nhi\u1ec7t \u0111\u1ed9 ph\u00f2ng, m\u00e0ng \u0111\u01b0\u1ee3c \u1ee7 qua \u0111\u00eam \u1edf 4\u00b0C v\u1edbi c\u00e1c kh\u00e1ng th\u1ec3 \u0111\u1eb7c hi\u1ec7u, ch\u1eb3ng h\u1ea1n nh\u01b0 GAPDH \u0111a d\u00f2ng c\u1ee7a th\u1ecf. Ph\u00e2n t\u00edch WB v\u1ec1 bi\u1ec3u hi\u1ec7n protein v\u00e0 qu\u00e1 tr\u00ecnh phosphoryl h\u00f3a \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n b\u1eb1ng c\u00e1ch s\u1eed d\u1ee5ng kh\u00e1ng th\u1ec3 ch\u1ed1ng l\u1ea1i AMPK, Parkin, PINK1, Akt, PI3K, Tom20 v\u00e0 GAPDH \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng l\u00e0m bi\u1ec7n ph\u00e1p ki\u1ec3m so\u00e1t n\u1ed9i b\u1ed9. C\u00e1c t\u00edn hi\u1ec7u c\u1ee5 th\u1ec3 \u0111\u01b0\u1ee3c hi\u1ec3n th\u1ecb b\u1eb1ng h\u1ec7 th\u1ed1ng t\u00e0i li\u1ec7u gel Bio-Rad (Ph\u00f2ng th\u00ed nghi\u1ec7m Bio-Rad, California, Hoa K\u1ef3). D\u1eef li\u1ec7u \u0111\u01b0\u1ee3c tr\u00ecnh b\u00e0y d\u01b0\u1edbi d\u1ea1ng trung b\u00ecnh \u00b1 SD (N<\/em>\u00a0= 3) v\u00e0 \u0111\u1ecbnh l\u01b0\u1ee3ng b\u1eb1ng ph\u00e2n t\u00edch ImageJ.<\/p>\n<\/div>\n

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Ch\u0103n nu\u00f4i<\/h3>\n

Chu\u1ed9t C57BL\/6 c\u00e1i 8 tu\u1ea7n tu\u1ed5i (SiPeiFu, B\u1eafc Kinh, Trung Qu\u1ed1c) \u0111\u00e3 \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng trong c\u00e1c th\u00ed nghi\u1ec7m. C\u00e1c con v\u1eadt \u0111\u01b0\u1ee3c nh\u1ed1t trong l\u1ed3ng v\u00e0 trong chu k\u1ef3 12 gi\u1edd s\u00e1ng\/12 gi\u1edd t\u1ed1i \u1edf \u0111\u1ed9 \u1ea9m 50% v\u00e0 25\u00b0C \u00b1 2\u00b0C. C\u00e1c con v\u1eadt \u0111\u01b0\u1ee3c c\u1ea5p mi\u1ec5n ph\u00ed ch\u1ebf \u0111\u1ed9 \u0103n vi\u00ean v\u00e0 n\u01b0\u1edbc u\u1ed1ng ti\u00eau chu\u1ea9n. Huy\u1ebft t\u01b0\u01a1ng thu \u0111\u01b0\u1ee3c b\u1eb1ng c\u00e1ch ly t\u00e2m \u1edf 200 g trong 10 ph\u00fat \u1edf 4\u00b0C v\u00e0 gi\u1eef \u1edf -80\u00b0C tr\u01b0\u1edbc khi chi\u1ebft.<\/p>\n

Vi\u1ec7c \u0111i\u1ec1u tra ph\u00f9 h\u1ee3p v\u1edbi\u00a0H\u01b0\u1edbng d\u1eabn ch\u0103m s\u00f3c v\u00e0 s\u1eed d\u1ee5ng \u0111\u1ed9ng v\u1eadt trong ph\u00f2ng th\u00ed nghi\u1ec7m<\/em>\u00a0do Vi\u1ec7n Y t\u1ebf Qu\u1ed1c gia Hoa K\u1ef3 xu\u1ea5t b\u1ea3n (\u1ea4n b\u1ea3n NIH s\u1ed1 85\u201323, s\u1eeda \u0111\u1ed5i 1985).<\/p>\n<\/div>\n

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Quy tr\u00ecnh th\u00ed nghi\u1ec7m tr\u00ean \u0111\u1ed9ng v\u1eadt<\/h3>\n

Nh\u1eefng con chu\u1ed9t \u0111\u01b0\u1ee3c ph\u00e2n ng\u1eabu nhi\u00ean v\u00e0o s\u00e1u nh\u00f3m \u0111i\u1ec1u tr\u1ecb, bao g\u1ed3m nh\u00f3m \u0111\u1ed1i ch\u1ee9ng, nh\u00f3m m\u00f4 h\u00ecnh (nh\u00f3m Dox), nh\u00f3m Dox + Brev ba li\u1ec1u v\u00e0 nh\u00f3m Dox + Dexra.<\/p>\n

\u0110\u1ec3 b\u1eaft ch\u01b0\u1edbc ch\u1ebf \u0111\u1ed9 \u0111i\u1ec1u tr\u1ecb c\u1ee7a con ng\u01b0\u1eddi, li\u1ec1u t\u00edch l\u0169y 12 mg\/kg Dox \u0111\u00e3 \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng.\u00a0th\u00f4ng qua<\/em>\u00a0ba m\u0169i ti\u00eam ip h\u00e0ng tu\u1ea7n (4 mg\/kg v\u00e0o c\u00e1c ng\u00e0y 0, 7 v\u00e0 14) ngo\u1ea1i tr\u1eeb nh\u00f3m \u0111\u1ed1i ch\u1ee9ng.<\/p>\n

\u0110\u1ec3 nghi\u00ean c\u1ee9u t\u00e1c d\u1ee5ng c\u1ee7a Brev\u00a0trong c\u01a1 th\u1ec3 s\u1ed1ng,<\/em>\u00a0chu\u1ed9t \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Brev, sau \u0111\u00f3 ti\u00eam ip h\u00e0ng ng\u00e0y 4,8 v\u00e0 16 mg\/kg Brev trong 3 tu\u1ea7n, v\u00e0 chu\u1ed9t trong nh\u00f3m \u0111i\u1ec1u tr\u1ecb Dox + Dexra nh\u1eadn \u0111\u01b0\u1ee3c 12 mg\/kg Dexra b\u1eb1ng c\u00e1ch ti\u00eam trong ph\u00fac m\u1ea1c trong 3 tu\u1ea7n ngo\u00e0i Dox s\u1ef1 \u0111\u1ed1i \u0111\u00e3i. (Alexandre v\u00e0 c\u1ed9ng s\u1ef1, 2020<\/a>). Brev v\u00e0 Dexra \u0111\u00e3 \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb sau khi ti\u00eam Dox. T\u1ef7 l\u1ec7 s\u1ed1ng s\u00f3t \u0111\u01b0\u1ee3c theo d\u00f5i h\u00e0ng ng\u00e0y v\u00e0 ch\u1ee9c n\u0103ng tim \u0111\u01b0\u1ee3c \u0111\u00e1nh gi\u00e1 b\u1eb1ng si\u00eau \u00e2m tim, 3 tu\u1ea7n sau l\u1ea7n ti\u00eam Dox \u0111\u1ea7u ti\u00ean (Li v\u00e0 c\u1ed9ng s\u1ef1, 2018<\/a>).<\/p>\n

Nh\u00f3m \u0111\u1ed1i ch\u1ee9ng \u0111\u01b0\u1ee3c ti\u00eam c\u00f9ng m\u1ed9t l\u01b0\u1ee3ng n\u01b0\u1edbc mu\u1ed1i b\u00ecnh th\u01b0\u1eddng. Nh\u1eefng con chu\u1ed9t \u0111\u00e3 b\u1ecb hy sinh 1 tu\u1ea7n sau khi d\u00f9ng Dox.<\/p>\n<\/div>\n

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Nghi\u00ean c\u1ee9u kh\u1ed1i u<\/h3>\n

Chu\u1ed9t \u0111\u01b0\u1ee3c ti\u00eam d\u01b0\u1edbi da 1\u00d7105<\/sup>\u00a0T\u1ebf b\u00e0o kh\u1ed1i u v\u00fa 4T1. M\u1ed9t tu\u1ea7n sau khi ti\u00eam t\u1ebf b\u00e0o, khi \u0111\u01b0\u1eddng k\u00ednh trung b\u00ecnh c\u1ee7a kh\u1ed1i u l\u1edbn h\u01a1n 2 mm, chu\u1ed9t \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox ho\u1eb7c breviscapine nh\u01b0 m\u00f4 t\u1ea3 tr\u01b0\u1edbc \u0111\u00e2y. K\u00edch th\u01b0\u1edbc kh\u1ed1i u \u0111\u01b0\u1ee3c \u0111o hai l\u1ea7n m\u1ed9t tu\u1ea7n trong t\u1ed1i \u0111a 4 tu\u1ea7n v\u00e0 kh\u1ed1i l\u01b0\u1ee3ng kh\u1ed1i u \u0111\u01b0\u1ee3c t\u00ednh theo ph\u01b0\u01a1ng tr\u00ecnh sau: V = 4\u03c0\/3\u00d7(L\/2)2\u00d7 (W\/2), trong \u0111\u00f3 V, L v\u00e0 W \u0111\u1ea1i di\u1ec7n cho th\u1ec3 t\u00edch, chi\u1ec1u d\u00e0i v\u00e0 chi\u1ec1u r\u1ed9ng c\u1ee7a kh\u1ed1i u t\u01b0\u01a1ng \u1ee9ng.<\/p>\n<\/div>\n

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18<\/sup>H\u00ecnh \u1ea3nh PET\/CT F-fluorodeoxyglucose<\/h3>\n

Chu\u1ed9t nh\u00f3m Dox v\u00e0 breviscapine (nh\u1ecbn \u0103n qua \u0111\u00eam) \u0111\u01b0\u1ee3c g\u00e2y m\u00ea b\u1eb1ng 2% isoflurane v\u00e0 ti\u00eam \u223c 11MBq\/0,2 ml PET fluorodeoxyglucose (FDG)\u00a0th\u00f4ng qua<\/em>\u00a0g\u00e2n \u0111u\u00f4i r\u1ed3i tr\u1edf v\u1ec1 chu\u1ed3ng. B\u1ed1n m\u01b0\u01a1i ph\u00fat sau, chu\u1ed9t \u0111\u01b0\u1ee3c g\u00e2y m\u00ea l\u1ea1i b\u1eb1ng 2% isoflurane v\u00e0 \u0111\u1eb7t tr\u00ean gi\u01b0\u1eddng \u0111\u1ecbnh v\u1ecb trong microPET Focus 220 (C\u00f4ng ty Siemens, Berlin, \u0110\u1ee9c). Sau \u0111\u00f3, qu\u00e1 tr\u00ecnh qu\u00e9t PET t\u0129nh 20 ph\u00fat \u0111\u00e3 \u0111\u01b0\u1ee3c b\u1eaft \u0111\u1ea7u. Sau \u0111\u00f3, chu\u1ed9t \u0111\u01b0\u1ee3c ch\u1ee5p \u1ea3nh trong microCAT II (C\u00f4ng ty Siemens, Berlin, \u0110\u1ee9c) \u1edf c\u01b0\u1eddng \u0111\u1ed9 ch\u00f9m tia X l\u00e0 180mA v\u00e0 \u0111i\u1ec7n \u00e1p \u1ed1ng tia X l\u00e0 80 kVp \u0111\u1ec3 \u0111\u1ed3ng \u0111\u0103ng k\u00fd gi\u1ea3i ph\u1eabu v\u1edbi h\u00ecnh \u1ea3nh PET.<\/p>\n<\/div>\n

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Ng\u01b0\u1eddi b\u1ec7nh<\/h3>\n

Sau h\u01a1n 4 gi\u1edd nh\u1ecbn \u0103n v\u00e0 \u0111\u1ea3m b\u1ea3o m\u1ee9c \u0111\u01b0\u1eddng huy\u1ebft d\u01b0\u1edbi 120 mg\/dl, t\u1ea5t c\u1ea3 b\u1ec7nh nh\u00e2n \u0111\u1ec1u \u0111\u01b0\u1ee3c ti\u00eam t\u0129nh m\u1ea1ch\u00a018<\/sup>F-FDG (5,5 MBq\/kg). Qu\u00e9t PET \/ CT \u0111\u01b0\u1ee3c b\u1eaft \u0111\u1ea7u 60 ph\u00fat sau khi ti\u00eam b\u1eb1ng ti\u1ec3u s\u1eed PET \/ CT k\u1ebft h\u1ee3p (C\u00f4ng ty Siemens, Berlin, \u0110\u1ee9c). T\u1ea5t c\u1ea3 c\u00e1c l\u1ea7n qu\u00e9t \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n trong m\u00f4 h\u00ecnh ba chi\u1ec1u. Ch\u1ee5p CT li\u1ec1u th\u1ea5p \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n tr\u01b0\u1edbc ti\u00ean \u0111\u1ec3 \u0111i\u1ec1u ch\u1ec9nh \u0111\u1ed9 \u0111\u1eadm nh\u1ea1t v\u00e0 t\u01b0\u01a1ng quan v\u1ec1 m\u1eb7t gi\u1ea3i ph\u1eabu. Gi\u1ea5y ch\u1ee9ng nh\u1eadn \u0111\u1ea1o \u0111\u1ee9c tu\u00e2n th\u1ee7 H\u01b0\u1edbng d\u1eabn ph\u00ea duy\u1ec7t t\u00e0i li\u1ec7u c\u1ee7a \u1ee6y ban \u0111\u1ea1o \u0111\u1ee9c do B\u1ec7nh vi\u1ec7n tr\u1ef1c thu\u1ed9c \u0110\u1ea1i h\u1ecdc Thanh \u0110\u1ea3o (QDU-HEC-2022057) xu\u1ea5t b\u1ea3n.<\/p>\n<\/div>\n

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Ph\u00e2n t\u00edch ch\u1ee9c n\u0103ng tim v\u00e0 m\u00f4 b\u1ec7nh h\u1ecdc<\/h3>\n

M\u00f4 tim chu\u1ed9t c\u1ee7a m\u1ed7i nh\u00f3m \u0111\u01b0\u1ee3c l\u01b0u tr\u1eef trong paraformaldehyde 4%, nh\u00fang trong s\u00e1p parafin v\u00e0 c\u1eaft n\u1ed1i ti\u1ebfp th\u00e0nh c\u00e1c ph\u1ea7n 4 mm. C\u00e1c ph\u1ea7n m\u00f4 \u0111\u00e3 \u0111\u01b0\u1ee3c kh\u1eed parafin\u00a0th\u00f4ng qua<\/em>\u00a0ng\u00e2m trong xylene (3 l\u1ea7n, m\u1ed7i l\u1ea7n 5 ph\u00fat) v\u00e0 \u0111\u01b0\u1ee3c b\u00f9 n\u01b0\u1edbc b\u1eb1ng c\u00e1ch s\u1eed d\u1ee5ng m\u1ed9t lo\u1ea1t r\u01b0\u1ee3u gi\u1ea3m d\u1ea7n (100%, 90%, 85% v\u00e0 75%, m\u1ed7i l\u1ea7n 5 ph\u00fat). C\u00e1c ph\u1ea7n \u0111\u01b0\u1ee3c nhu\u1ed9m b\u1eb1ng hematoxylin v\u00e0 eosin \u0111\u1ec3 ph\u00e2n t\u00edch m\u00f4 h\u1ecdc. C\u00e1c m\u1eabu sinh thi\u1ebft \u0111\u01b0\u1ee3c nhu\u1ed9m b\u1eb1ng thu\u1ed1c nhu\u1ed9m ba m\u00e0u c\u1ee7a Masson \u0111\u1ec3 \u0111i\u1ec1u tra b\u1ea5t k\u1ef3 thay \u0111\u1ed5i h\u00ecnh th\u00e1i v\u00e0 x\u01a1 h\u00f3a n\u00e0o trong tim. Nhu\u1ed9m m\u00e0u xanh th\u1ec3 hi\u1ec7n s\u1ef1 t\u00edch t\u1ee5 collagen. H\u00f3a m\u00f4 mi\u1ec5n d\u1ecbch \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n b\u1eb1ng b\u1ed9 d\u1ee5ng c\u1ee5 nhu\u1ed9m Histone Simple (Nichirei, Tokyo, Nh\u1eadt B\u1ea3n) theo h\u01b0\u1edbng d\u1eabn c\u1ee7a nh\u00e0 s\u1ea3n xu\u1ea5t. C\u00e1c ph\u1ea7n \u0111\u01b0\u1ee3c x\u1eed l\u00fd trong 15 ph\u00fat v\u1edbi 3% H2O2 trong metanol \u0111\u1ec3 l\u00e0m b\u1ea5t ho\u1ea1t peroxidase n\u1ed9i sinh v\u00e0 sau \u0111\u00f3 \u0111\u01b0\u1ee3c \u1ee7 \u1edf nhi\u1ec7t \u0111\u1ed9 ph\u00f2ng trong 1 gi\u1edd v\u1edbi kh\u00e1ng th\u1ec3 ch\u00ednh IL-1, 1:100. C\u01a1 s\u1edf h\u1ea1 t\u1ea7ng sau \u0111\u00f3 \u0111\u01b0\u1ee3c quan s\u00e1t \u1edf \u0111\u1ed9 ph\u00f3ng \u0111\u1ea1i 20 l\u1ea7n b\u1eb1ng k\u00ednh hi\u1ec3n vi hu\u1ef3nh quang \u0111\u1ea3o ng\u01b0\u1ee3c CMS GmbH c\u1ee7a Leica Microsystems (Leica Camera AG, Barnack, \u0110\u1ee9c).<\/p>\n<\/div>\n

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\u0110o n\u1ed3ng \u0111\u1ed9 glucose<\/h3>\n

Chu\u1ed9t \u0111\u01b0\u1ee3c duy tr\u00ec ch\u1ebf \u0111\u1ed9 \u0103n chow b\u00ecnh th\u01b0\u1eddng. V\u00e0o ng\u00e0y th\u00ed nghi\u1ec7m, chu\u1ed9t \u0111\u01b0\u1ee3c nh\u1ecbn \u0111\u00f3i trong 6 gi\u1edd (b\u1eaft \u0111\u1ea7u l\u00fac 8 gi\u1edd s\u00e1ng) v\u00e0 l\u1ea5y m\u00e1u.\u00a0th\u00f4ng qua<\/em>\u00a0t\u0129nh m\u1ea1ch \u0111u\u00f4i \u0111\u1ec3 \u0111o n\u1ed3ng \u0111\u1ed9 glucose.<\/p>\n

T\u1ebf b\u00e0o nguy\u00ean b\u00e0o c\u01a1 tim chu\u1ed9t H9c2 \u0111\u01b0\u1ee3c r\u1eeda b\u1eb1ng dung d\u1ecbch mu\u1ed1i \u0111\u1ec7m ph\u1ed1t ph\u00e1t (PBS), ly t\u00e2m v\u00e0 nghi\u1ec1n n\u00e1t b\u1eb1ng si\u00eau \u00e2m, r\u1ed3i \u1ee7 trong \u0111i\u1ec1u ki\u1ec7n nu\u00f4i c\u1ea5y t\u1ebf b\u00e0o ti\u00eau chu\u1ea9n trong 10 ph\u00fat. Sau khi \u1ee7, \u0111\u1ed9 h\u1ea5p th\u1ee5 \u0111\u01b0\u1ee3c \u0111o b\u1eb1ng m\u00e1y \u0111\u1ecdc vi \u0111\u0129a (Perkin Elmer, Massachusetts, Hoa K\u1ef3).<\/p>\n<\/div>\n

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X\u00e9t nghi\u1ec7m h\u1ea5p th\u1ee5 mi\u1ec5n d\u1ecbch li\u00ean k\u1ebft v\u1edbi enzyme<\/h3>\n

M\u00f4 chu\u1ed9t \u0111\u01b0\u1ee3c ly gi\u1ea3i b\u1eb1ng dung d\u1ecbch \u0111\u1ec7m ly gi\u1ea3i. C\u00e1c m\u1eabu \u0111\u01b0\u1ee3c c\u00e1ch \u00e2m b\u1eb1ng m\u00e1y \u0111\u1ed3ng nh\u1ea5t Qsonica s\u1eed d\u1ee5ng xung 30 Hz trong 20 gi\u00e2y v\u00e0 sau \u0111\u00f3 ly t\u00e2m \u1edf t\u1ed1c \u0111\u1ed9 12.000 g trong 10 ph\u00fat. Ph\u1ea7n n\u1ed5i ph\u00eda tr\u00ean \u0111\u01b0\u1ee3c thu th\u1eadp, chia th\u00e0nh c\u00e1c l\u1ecd 200 \u00b5l v\u00e0 \u0111\u01b0\u1ee3c b\u1ea3o qu\u1ea3n \u1edf -80\u00b0C. N\u1ed3ng \u0111\u1ed9 protein c\u1ee7a c\u00e1c m\u1eabu \u0111\u01b0\u1ee3c \u0111\u1ecbnh l\u01b0\u1ee3ng b\u1eb1ng x\u00e9t nghi\u1ec7m BCA. C\u00e1c m\u1eabu \u0111\u01b0\u1ee3c ph\u00e2n t\u00edch b\u1eb1ng c\u00e1ch s\u1eed d\u1ee5ng b\u1ed9 x\u00e9t nghi\u1ec7m h\u1ea5p th\u1ee5 mi\u1ec5n d\u1ecbch li\u00ean k\u1ebft enzyme \u0111\u1ec3 t\u00ecm TNF-\u03b1, IL-1\u03b2 v\u00e0 IL-6 theo quy tr\u00ecnh c\u1ee7a nh\u00e0 s\u1ea3n xu\u1ea5t. M\u1eadt \u0111\u1ed9 quang \u0111\u01b0\u1ee3c \u0111o \u1edf b\u01b0\u1edbc s\u00f3ng 450nm b\u1eb1ng c\u00e1ch s\u1eed d\u1ee5ng \u0111\u1ea7u \u0111\u1ecdc vi b\u1ea3n VICTOR Nivo \u2122 (Perkin Elmer, Massachusetts, Hoa K\u1ef3).<\/p>\n<\/div>\n

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X\u00e1c \u0111\u1ecbnh s\u1ef1 thay \u0111\u1ed5i trong h\u1ec7 th\u1ed1ng trao \u0111\u1ed5i ch\u1ea5t c\u1ee7a chu\u1ed9t<\/h3>\n

C\u00e1c m\u1eabu m\u00e1u \u0111\u01b0\u1ee3c h\u00f2a l\u1ea1i, \u1ee7 tr\u00ean \u0111\u00e1, ly t\u00e2m, pha lo\u00e3ng \u0111\u1ebfn n\u1ed3ng \u0111\u1ed9 cu\u1ed1i c\u00f9ng v\u00e0 ly t\u00e2m. Cu\u1ed1i c\u00f9ng, ch\u1ea5t n\u1ed5i ph\u00eda tr\u00ean \u0111\u01b0\u1ee3c b\u01a1m v\u00e0o h\u1ec7 th\u1ed1ng LC-MS\/MS \u0111\u1ec3 ph\u00e2n t\u00edch. C\u00e1c ph\u00e2n t\u00edch UHPLC\u2013MS\/MS \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n b\u1eb1ng h\u1ec7 th\u1ed1ng Vanquish UHPLC (Thermo Fisher, Massachusetts, Hoa K\u1ef3) k\u1ebft h\u1ee3p v\u1edbi Orbitrap Q ExactiveTM<\/sup>\u00a0M\u00e1y quang ph\u1ed5 kh\u1ed1i HF (Thermo Fisher, Massachusetts, Hoa K\u1ef3). C\u00e1c ch\u1ea5t chuy\u1ec3n h\u00f3a \u0111\u01b0\u1ee3c x\u00e1c \u0111\u1ecbnh \u0111\u00e3 \u0111\u01b0\u1ee3c ch\u00fa th\u00edch b\u1eb1ng c\u01a1 s\u1edf d\u1eef li\u1ec7u KEGG, c\u01a1 s\u1edf d\u1eef li\u1ec7u HMDB v\u00e0 c\u01a1 s\u1edf d\u1eef li\u1ec7u B\u1ea3n \u0111\u1ed3 LIPID. Ph\u00e2n t\u00edch th\u00e0nh ph\u1ea7n ch\u00ednh (PCA) v\u00e0 ph\u00e2n t\u00edch ph\u00e2n bi\u1ec7t b\u00ecnh ph\u01b0\u01a1ng nh\u1ecf nh\u1ea5t m\u1ed9t ph\u1ea7n (PLS-DA) \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n b\u1eb1ng metaX. Ch\u00fang t\u00f4i \u0111\u00e3 \u00e1p d\u1ee5ng ph\u00e2n t\u00edch \u0111\u01a1n bi\u1ebfn (t<\/em>-test) \u0111\u1ec3 t\u00ednh \u00fd ngh\u0129a th\u1ed1ng k\u00ea (P<\/em>-gi\u00e1 tr\u1ecb). Ch\u1ea5t chuy\u1ec3n h\u00f3a c\u00f3 VIP>1,\u00a0P<\/em>\u00a0gi\u00e1 tr\u1ecb <0,05 v\u00e0 thay \u0111\u1ed5i l\u1ea7n \u22652 ho\u1eb7c 0,5 \u0111\u01b0\u1ee3c coi l\u00e0 c\u00e1c ch\u1ea5t chuy\u1ec3n h\u00f3a phong ph\u00fa kh\u00e1c nhau.<\/p>\n<\/div>\n

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Ph\u00e2n t\u00edch th\u1ed1ng k\u00ea<\/h3>\n

Ph\u00e2n t\u00edch th\u1ed1ng k\u00ea \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n b\u1eb1ng ANOVA v\u1edbi IBM SPSS Statistic (V19.0, America). D\u1eef li\u1ec7u \u0111\u01b0\u1ee3c tr\u00ecnh b\u00e0y d\u01b0\u1edbi d\u1ea1ng trung b\u00ecnh \u00b1 SD (N<\/em>\u00a0= 6\u20139).\u00a0P<\/em>\u00a0< 0,05 \u0111\u01b0\u1ee3c coi l\u00e0 \u0111\u00e1ng k\u1ec3.<\/p>\n<\/div>\n<\/div>\n

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\u0110i \u0111\u1ebfn:<\/a><\/div>\n

K\u1ebft qu\u1ea3<\/h2>\n
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Anthracycline l\u00e0m gi\u1ea3m chuy\u1ec3n h\u00f3a glucose c\u1ee7a c\u01a1 tim v\u00e0 t\u0103ng s\u1eed d\u1ee5ng axit b\u00e9o<\/h3>\n

\u0110\u1ea7u ti\u00ean ch\u00fang t\u00f4i nghi\u00ean c\u1ee9u\u00a018<\/sup>H\u00ecnh \u1ea3nh F-FDG PET\/CT v\u1ec1 tim c\u1ee7a b\u1ec7nh nh\u00e2n \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng h\u00f3a tr\u1ecb li\u1ec7u anthracycline v\u00e0 b\u1ec7nh nh\u00e2n kh\u00f4ng d\u00f9ng h\u00f3a tr\u1ecb li\u1ec7u v\u00e0 ph\u00e2n t\u00edch d\u1eef li\u1ec7u cho th\u1ea5y (H\u00ecnh 1A<\/a>) xu h\u01b0\u1edbng gi\u1ea3m h\u1ea5p thu glucose \u1edf c\u01a1 tim \u1edf b\u1ec7nh nh\u00e2n \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng h\u00f3a tr\u1ecb. Ch\u00fang t\u00f4i d\u1ef1 \u0111o\u00e1n r\u1eb1ng nh\u1eefng thay \u0111\u1ed5i trong th\u00f4ng s\u1ed1 n\u00e0y c\u00f3 th\u1ec3 t\u01b0\u01a1ng quan v\u1edbi t\u00ecnh tr\u1ea1ng nhi\u1ec5m \u0111\u1ed9c tim do anthracycline g\u00e2y ra. \u0110\u1ec3 x\u00e1c minh m\u1ed1i li\u00ean h\u1ec7 n\u1ed9i t\u1ea1i gi\u1eefa c\u00e1c b\u1ea5t th\u01b0\u1eddng v\u1ec1 chuy\u1ec3n h\u00f3a v\u00e0 DIC, ch\u00fang t\u00f4i \u0111\u00e3 thi\u1ebft l\u1eadp m\u00f4 h\u00ecnh chu\u1ed9t DIC do Dox g\u00e2y ra v\u00e0\u00a018<\/sup>K\u1ebft qu\u1ea3 F-FDG PET cho th\u1ea5y s\u1ef1 h\u1ea5p thu c\u1ee7a tim \u1edf chu\u1ed9t \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox th\u1ea5p h\u01a1n \u0111\u00e1ng k\u1ec3 so v\u1edbi chu\u1ed9t kh\u00f4ng \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb sau 4 tu\u1ea7n (H\u00ecnh 1B<\/a>). \u0110i\u1ec1u n\u00e0y cho th\u1ea5y anthracycline \u1ea3nh h\u01b0\u1edfng \u0111\u1ebfn chuy\u1ec3n h\u00f3a glucose c\u1ee7a c\u01a1 tim \u1edf c\u1ea3 b\u1ec7nh nh\u00e2n v\u00e0 m\u00f4 h\u00ecnh chu\u1ed9t.<\/p>\n

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<\/div>\n

\"An<\/a><\/div>\n

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H\u00ccNH 1<\/a><\/div>\n
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(M\u1ed8T)<\/strong>\u00a0N\u1ed3ng \u0111\u1ed9 c\u1ee7a\u00a018<\/sup>F-FDG \u0111\u01b0\u1ee3c tim c\u1ee7a b\u1ec7nh nh\u00e2n \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng h\u00f3a tr\u1ecb v\u00e0 kh\u00f4ng h\u00f3a tr\u1ecb ti\u1ebfp nh\u1eadn.\u00a0(B)<\/strong>\u00a018<\/sup>Thu th\u1eadp h\u00ecnh \u1ea3nh F-FDG PET\/CT v\u00e0 tim m\u1ea1ch\u00a018<\/sup>S\u1ef1 h\u1ea5p thu F-FDG.\u00a0(C)<\/strong>\u00a0B\u1ea3n \u0111\u1ed3 nhi\u1ec7t c\u1ee7a chu\u1ed9t \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox.\u00a0(D)<\/strong>\u00a0N\u1ed9i dung MDA trong c\u00e1c \u00f4 H9c2.\u00a0(E)<\/strong>\u00a0Nhu\u1ed9m HE cho th\u1ea5y Dox \u0111\u00e3 l\u00e0m gi\u1ea3m k\u00edch th\u01b0\u1edbc t\u1ebf b\u00e0o c\u01a1 tim. Ki\u1ec3m so\u00e1t so v\u1edbi Dox: ***P<\/em>\u00a0< 0,0005, **P<\/em>\u00a0< 0,005, *P<\/em>\u00a0< 0,05, trung b\u00ecnh \u00b1 SD.\u00a0N<\/em>\u00a0= 6\u20139.<\/p>\n<\/div>\n<\/div>\n<\/div>\n

Trong \u0111i\u1ec1u ki\u1ec7n b\u00ecnh th\u01b0\u1eddng, c\u01a1 tim ch\u1ee7 y\u1ebfu s\u1eed d\u1ee5ng \u0111\u01b0\u1eddng v\u00e0 lipid \u0111\u1ec3 cung c\u1ea5p n\u0103ng l\u01b0\u1ee3ng, trong \u0111\u00f3 \u0111\u01b0\u1eddng v\u00e0 lipid chi\u1ebfm l\u1ea7n l\u01b0\u1ee3t kho\u1ea3ng 20%\u201330% v\u00e0 60% n\u0103ng l\u01b0\u1ee3ng c\u1ee7a c\u01a1 tim; h\u01a1n n\u1eefa, glucose hi\u1ec7u qu\u1ea3 h\u01a1n trong vi\u1ec7c s\u1ea3n xu\u1ea5t ATP (Thi\u1ec7u v\u00e0 Thi\u00ean, 2015<\/a>). L\u00e0m th\u1ebf n\u00e0o tim th\u00edch nghi v\u1edbi vi\u1ec7c \u0111\u1ecbnh h\u00ecnh l\u1ea1i qu\u00e1 tr\u00ecnh chuy\u1ec3n h\u00f3a n\u0103ng l\u01b0\u1ee3ng trong c\u01a1 tim b\u1eb1ng c\u00e1c can thi\u1ec7p h\u00f3a tr\u1ecb li\u1ec7u v\u00e0 li\u1ec7u nh\u1eefng thay \u0111\u1ed5i \u0111\u00f3 c\u00f3 \u1ea3nh h\u01b0\u1edfng \u0111\u1ebfn c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i c\u1ee7a tim v\u00e0 d\u1eabn \u0111\u1ebfn s\u1ef1 ph\u00e1t tri\u1ec3n c\u1ee7a DIC hay kh\u00f4ng v\u1eabn ch\u01b0a r\u00f5 r\u00e0ng. B\u1eb1ng c\u00e1ch ph\u00e2n t\u00edch d\u1eef li\u1ec7u trao \u0111\u1ed5i ch\u1ea5t t\u1eeb chu\u1ed9t (H\u00ecnh 1C<\/a>), ch\u00fang t\u00f4i nh\u1eadn th\u1ea5y r\u1eb1ng c\u00e1c ch\u1ea5t chuy\u1ec3n h\u00f3a cho th\u1ea5y m\u1ee9c \u0111\u1ed9 t\u0103ng l\u00ean sau khi ti\u1ebfp x\u00fac v\u1edbi Dox ch\u1ee7 y\u1ebfu li\u00ean quan \u0111\u1ebfn vi\u1ec7c ph\u00e2n lo\u1ea1i lipid v\u00e0 vi\u1ec7c gi\u1ea3m m\u1ee9c \u0111\u1ed9 c\u1ee7a c\u00e1c ch\u1ec9 s\u1ed1 chuy\u1ec3n h\u00f3a glucose nh\u01b0 D-glucose-6-phosphate v\u00e0 AKG l\u00e0 r\u00f5 r\u00e0ng. H\u01a1n n\u1eefa, ph\u00e2n t\u00edch l\u00e0m gi\u00e0u KEGG cho th\u1ea5y con \u0111\u01b0\u1eddng trao \u0111\u1ed5i ch\u1ea5t lipid b\u1ecb thay \u0111\u1ed5i \u0111\u00e1ng k\u1ec3 sau khi ti\u1ebfp x\u00fac v\u1edbi Dox (H\u00ecnh b\u1ed5 sung S1<\/a>). M\u1ee9c \u0111\u1ed9 ch\u1ea5t chuy\u1ec3n h\u00f3a MDA c\u1ee7a FAO trong c\u01a1 tim (H\u00ecnh 1D<\/a>) \u0111\u00e3 t\u0103ng \u0111\u00e1ng k\u1ec3 sau khi \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox. \u0110i\u1ec1u n\u00e0y cho th\u1ea5y qu\u00e1 tr\u00ecnh chuy\u1ec3n h\u00f3a glucose \u1edf tim b\u1ecb suy gi\u1ea3m sau khi can thi\u1ec7p Dox v\u00e0 \u0111\u01b0\u1ee3c thay th\u1ebf b\u1eb1ng qu\u00e1 tr\u00ecnh \u0111\u1ed1t ch\u00e1y lipid t\u0103ng l\u00ean, \u0111i\u1ec1u n\u00e0y t\u01b0\u01a1ng \u0111\u1ed1i \u00edt ti\u1ebft ki\u1ec7m n\u0103ng l\u01b0\u1ee3ng h\u01a1n. S\u1ef1 chuy\u1ec3n h\u00f3a lipid kh\u00f4ng \u0111\u1ea7y \u0111\u1ee7 n\u00e0y g\u00e2y ra s\u1ef1 t\u00edch t\u1ee5 m\u1ed9t l\u01b0\u1ee3ng l\u1edbn lipid trong c\u01a1 tim v\u00e0 nhu\u1ed9m b\u1ec7nh l\u00fd cho th\u1ea5y m\u1ed9t s\u1ed1 l\u01b0\u1ee3ng l\u1edbn kh\u00f4ng b\u00e0o lipid trong tim c\u1ee7a \u0111\u1ed9ng v\u1eadt ti\u1ebfp x\u00fac v\u1edbi Dox, d\u1eabn \u0111\u1ebfn t\u00ecnh tr\u1ea1ng tim nhi\u1ec5m m\u1ee1 (H\u00ecnh 1E<\/a>).<\/p>\n<\/div>\n

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Anthracycline l\u00e0m t\u0103ng ti\u00eau th\u1ee5 oxy c\u1ee7a c\u01a1 tim v\u00e0 gi\u1ea3m t\u1ed1c \u0111\u1ed9 s\u1ea3n xu\u1ea5t ATP<\/h3>\n

\u0110i\u1ec1u th\u00fa v\u1ecb l\u00e0 s\u1ef1 b\u00f9 tr\u1eeb trao \u0111\u1ed5i ch\u1ea5t n\u00e0y l\u00e0m t\u0103ng n\u1ed3ng \u0111\u1ed9 ROS c\u1ee7a c\u01a1 tim, d\u1eabn \u0111\u1ebfn c\u0103ng th\u1eb3ng oxy h\u00f3a cao h\u01a1n (H\u00ecnh 2A<\/a>). Ph\u00e2n t\u00edch chuy\u1ec3n h\u00f3a n\u0103ng l\u01b0\u1ee3ng O2K cho th\u1ea5y Dox l\u00e0m t\u0103ng m\u1ee9c ti\u00eau th\u1ee5 oxy c\u1ee7a c\u01a1 tim (H\u00ecnh 2B<\/a>) v\u00e0 d\u1eabn \u0111\u1ebfn s\u1ef1 si\u00eau ph\u00e2n c\u1ef1c c\u1ee7a m\u00e0ng ty th\u1ec3 (H\u00ecnh 2C<\/a>) (\u0111\u00e2y c\u0169ng l\u00e0 d\u1ea5u hi\u1ec7u c\u1ee7a m\u1ee9c \u0111\u1ed9 c\u0103ng th\u1eb3ng oxy h\u00f3a ty th\u1ec3 t\u0103ng cao v\u00e0 th\u01b0\u1eddng th\u1ea5y trong c\u00e1c m\u00f4 h\u00ecnh t\u00e1i t\u01b0\u1edbi m\u00e1u-thi\u1ebfu m\u00e1u c\u1ee5c b\u1ed9 c\u01a1 tim). Nhu\u1ed9m JC-1 c\u0169ng cho th\u1ea5y ph\u01a1i nhi\u1ec5m Dox g\u00e2y ra s\u1ef1 gia t\u0103ng \u0111i\u1ec7n th\u1ebf m\u00e0ng (c\u01b0\u1eddng \u0111\u1ed9 hu\u1ef3nh quang \u0111\u1ecf t\u0103ng c\u01b0\u1eddng) \u1edf m\u1ed9t s\u1ed1 t\u1ebf b\u00e0o s\u1ed1ng s\u00f3t (H\u00ecnh 2D<\/a>). M\u1eb7c d\u00f9 c\u00e1c qu\u00e1 tr\u00ecnh b\u00f9 tr\u1eeb nh\u01b0 t\u0103ng ti\u00eau th\u1ee5 oxy v\u00e0 oxy h\u00f3a lipid x\u1ea3y ra \u1edf tim, nh\u01b0ng th\u1eadt kh\u00f4ng may, t\u1ed1c \u0111\u1ed9 s\u1ea3n xu\u1ea5t ATP trong c\u01a1 tim \u0111\u00e3 gi\u1ea3m \u0111\u00e1ng k\u1ec3 \u0111\u1ec3 \u0111\u00e1p \u1ee9ng v\u1edbi vi\u1ec7c gi\u1ea3m chuy\u1ec3n h\u00f3a glucose (H\u00ecnh 2E<\/a>). So s\u00e1nh t\u1ed1c \u0111\u1ed9 ti\u00eau th\u1ee5 oxy v\u00e0 t\u1ed1c \u0111\u1ed9 s\u1ea3n xu\u1ea5t ATP cho th\u1ea5y ph\u01a1i nhi\u1ec5m Dox d\u1eabn \u0111\u1ebfn c\u01a1 tim ti\u00eau th\u1ee5 m\u1ed9t l\u01b0\u1ee3ng l\u1edbn oxy nh\u01b0ng ch\u1ec9 s\u1ea3n xu\u1ea5t m\u1ed9t l\u01b0\u1ee3ng nh\u1ecf ATP (H\u00ecnh 2F<\/a>), l\u00e0m t\u0103ng \u0111\u00e1ng k\u1ec3 g\u00e1nh n\u1eb7ng cho tim. S\u1ef1 thi\u1ebfu h\u1ee5t n\u0103ng l\u01b0\u1ee3ng \u0111\u1ea7u ra n\u00e0y g\u00e2y ra s\u1ef1 gia t\u0103ng \u0111\u00e1ng k\u1ec3 m\u1ee9c \u0111\u1ed9 AMPK c\u1ee7a th\u1ee5 th\u1ec3 n\u0103ng l\u01b0\u1ee3ng trong nh\u00f3m Dox (H\u00ecnh 2G<\/a>). Do \u0111\u00f3, ch\u00fang t\u00f4i \u0111\u01b0a ra gi\u1ea3 thuy\u1ebft r\u1eb1ng tim c\u00f3 t\u1ed1c \u0111\u1ed9 ti\u00eau th\u1ee5 oxy cao v\u00e0 t\u1ed1c \u0111\u1ed9 s\u1ea3n xu\u1ea5t ATP th\u1ea5p \u0111\u1ec3 \u0111\u00e1p \u1ee9ng v\u1edbi s\u1ef1 suy gi\u1ea3m chuy\u1ec3n h\u00f3a glucose do anthracycline g\u00e2y ra v\u00e0 hi\u1ec7n t\u01b0\u1ee3ng n\u00e0y kh\u00f4ng \u0111\u00e1p \u1ee9ng \u0111\u1ea7y \u0111\u1ee7 nhu c\u1ea7u n\u0103ng l\u01b0\u1ee3ng c\u1ee7a c\u01a1 tim m\u00e0 d\u1eabn \u0111\u1ebfn c\u0103ng th\u1eb3ng oxy h\u00f3a qu\u00e1 m\u1ee9c. Do \u0111\u00f3, ng\u01b0\u1eddi ta suy \u0111o\u00e1n r\u1eb1ng \u0111\u1ec3 \u0111\u00e1p \u1ee9ng v\u1edbi kho\u1ea3ng tr\u1ed1ng n\u0103ng l\u01b0\u1ee3ng, qu\u00e1 tr\u00ecnh oxy h\u00f3a lipid trong tim t\u0103ng l\u00ean v\u00e0 t\u00edch l\u0169y nhi\u1ec1u ROS h\u01a1n, v\u00e0 con \u0111\u01b0\u1eddng ph\u1ea3n h\u1ed3i k\u00e9m n\u00e0y c\u00f3 th\u1ec3 l\u00e0 \u0111\u1ed9ng l\u1ef1c quan tr\u1ecdng c\u1ee7a DIC.<\/p>\n

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\"An<\/a><\/div>\n

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H\u00ccNH 2<\/a><\/div>\n
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(M\u1ed8T)<\/strong>\u00a0C\u01b0\u1eddng \u0111\u1ed9 nhu\u1ed9m ROS trong c\u00e1c t\u1ebf b\u00e0o H9c2.\u00a0(B)<\/strong>\u00a0Ti\u00eau th\u1ee5 oxy c\u1ee7a tim trong c\u00e1c t\u1ebf b\u00e0o H9c2.\u00a0(C)<\/strong>\u00a0Ti\u1ec1m n\u0103ng m\u00e0ng ty th\u1ec3.\u00a0(D)<\/strong>\u00a0Bi\u1ec3u \u0111\u1ed3 thanh v\u00e0 nhu\u1ed9m m\u00e0u JC-1.\u00a0(E)<\/strong>\u00a0H\u00e0m l\u01b0\u1ee3ng ATP trong c\u00e1c t\u1ebf b\u00e0o H9c2.\u00a0(F)<\/strong>\u00a0T\u1ef7 l\u1ec7 s\u1ea3n xu\u1ea5t\/ti\u00eau th\u1ee5 oxy c\u1ee7a ATP trong t\u1ebf b\u00e0o H9c2.\u00a0(G)<\/strong>\u00a0M\u1ee9c \u0111\u1ed9 bi\u1ec3u hi\u1ec7n c\u1ee7a AMPK v\u00e0 \u03b2-tubulin \u0111\u00e3 \u0111\u01b0\u1ee3c \u0111o\u00a0trong \u1ed1ng nghi\u1ec7m<\/em>\u00a0c\u1ee7a WB. Ki\u1ec3m so\u00e1t so v\u1edbi Dox: ***P<\/em>\u00a0< 0,0005, **P<\/em>\u00a0< 0,005, *P<\/em>\u00a0< 0,05, trung b\u00ecnh \u00b1 SD.\u00a0N<\/em>\u00a0= 6\u20139.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n

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Ch\u1ea5t b\u1ea3o v\u1ec7 tim m\u1ea1ch m\u1edbi breviscapine th\u00fac \u0111\u1ea9y chuy\u1ec3n h\u00f3a glucose \u1edf tim v\u00e0 \u1ee9c ch\u1ebf b\u1ec7nh c\u01a1 tim do Dox g\u00e2y ra<\/h3>\n

L\u1ea5y c\u1ea3m h\u1ee9ng t\u1eeb c\u00e1c k\u1ebft qu\u1ea3 n\u00f3i tr\u00ean, ch\u00fang t\u00f4i \u0111\u00e3 nghi\u00ean c\u1ee9u t\u00e1c d\u1ee5ng b\u1ea3o v\u1ec7 c\u1ee7a flavonoid breviscapine, \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng \u0111\u1ec3 \u0111i\u1ec1u tr\u1ecb c\u00e1c b\u1ec7nh tim m\u1ea1ch, ch\u1ed1ng l\u1ea1i s\u1ef1 ti\u1ebfn tri\u1ec3n c\u1ee7a DIC t\u1eeb g\u00f3c \u0111\u1ed9 trao \u0111\u1ed5i ch\u1ea5t. Giao th\u1ee9c th\u1eed nghi\u1ec7m \u0111\u01b0\u1ee3c hi\u1ec3n th\u1ecb trong\u00a0H\u00ecnh 3A<\/a>, V\u00e0\u00a018<\/sup>H\u00ecnh \u1ea3nh F-FDG PET\/CT \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n b\u1eb1ng chu\u1ed9t 1 tu\u1ea7n sau l\u1ea7n ti\u00eam Doxorubicin \u0111\u1ea7u ti\u00ean. Nh\u01b0 th\u1ec3 hi\u1ec7n trong\u00a0H\u00ecnh 3B<\/a>, s\u1ef1 h\u1ea5p thu c\u1ee7a tim \u1edf nh\u00f3m \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng breviscapine cao h\u01a1n \u0111\u00e1ng k\u1ec3 so v\u1edbi nh\u00f3m \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox, cho th\u1ea5y r\u1eb1ng can thi\u1ec7p b\u1eb1ng breviscapine c\u00f3 th\u1ec3 \u0111\u1ea3o ng\u01b0\u1ee3c s\u1ef1 gi\u1ea3m chuy\u1ec3n h\u00f3a glucose c\u1ee7a tim do Dox g\u00e2y ra v\u00e0 \u0111i\u1ec1u ch\u1ec9nh l\u1ea1i qu\u00e1 tr\u00ecnh chuy\u1ec3n h\u00f3a n\u0103ng l\u01b0\u1ee3ng c\u1ee7a tim. Ch\u1ee9c n\u0103ng tim v\u00e0 nh\u1eefng thay \u0111\u1ed5i b\u1ec7nh l\u00fd sau khi \u0111i\u1ec1u tr\u1ecb b\u1eb1ng breviscapine \u0111\u01b0\u1ee3c ki\u1ec3m tra ti\u1ebfp theo v\u00e0 thu\u1ed1c l\u00e2m s\u00e0ng dexrazoxane (Dexra) \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng l\u00e0m \u0111\u1ed1i ch\u1ee9ng d\u01b0\u01a1ng t\u00ednh. Si\u00eau \u00e2m tim \u1edf\u00a0H\u00ecnh 3C<\/a>\u00a0cho th\u1ea5y LVEF v\u00e0 LVFS \u1edf nh\u00f3m Dox th\u1ea5p h\u01a1n \u0111\u00e1ng k\u1ec3 so v\u1edbi nh\u00f3m \u0111\u1ed1i ch\u1ee9ng v\u00e0 LVESV v\u00e0 LVD cao h\u01a1n \u0111\u00e1ng k\u1ec3 so v\u1edbi nh\u00f3m \u0111\u1ed1i ch\u1ee9ng. Nh\u1eefng k\u1ebft qu\u1ea3 n\u00e0y cho th\u1ea5y ch\u1ee9c n\u0103ng t\u00e2m thu th\u1ea5t tr\u00e1i c\u1ee7a chu\u1ed9t gi\u1ea3m sau khi \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox v\u00e0 t\u1ed5n th\u01b0\u01a1ng c\u01a1 tim do Dox g\u00e2y ra trong nghi\u00ean c\u1ee9u n\u00e0y t\u01b0\u01a1ng t\u1ef1 nh\u01b0 b\u1ec7nh c\u01a1 tim gi\u00e3n n\u1edf. Dox l\u00e0m gi\u1ea3m ch\u1ee9c n\u0103ng t\u00e2m thu, t\u01b0\u01a1ng t\u1ef1 nh\u01b0 nh\u1eefng g\u00ec \u0111\u00e3 \u0111\u01b0\u1ee3c b\u00e1o c\u00e1o tr\u01b0\u1edbc \u0111\u00e2y (Venturini v\u00e0 c\u1ed9ng s\u1ef1, 1996<\/a>;\u00a0Sun v\u00e0 c\u1ed9ng s\u1ef1, 2022<\/a>). T\u1ea5t c\u1ea3 c\u00e1c ch\u1ee9c n\u0103ng \u0111\u00e3 \u0111\u01b0\u1ee3c ph\u1ee5c h\u1ed3i \u1edf tim c\u1ee7a \u0111\u1ed9ng v\u1eadt \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Brev v\u00e0 Dox so v\u1edbi tim c\u1ee7a \u0111\u1ed9ng v\u1eadt ch\u1ec9 \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng doxorubicin. cTnI l\u00e0 d\u1ea5u \u1ea5n sinh h\u1ecdc c\u1ee7a t\u1ed5n th\u01b0\u01a1ng c\u01a1 tim (Solaro v\u00e0 Solaro, 2020<\/a>). N\u1ed3ng \u0111\u1ed9 cTnI t\u0103ng \u0111\u00e1ng k\u1ec3 \u1edf nh\u1eefng con chu\u1ed9t \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng doxorubicin \u0111\u01a1n thu\u1ea7n so v\u1edbi nh\u1eefng con trong nh\u00f3m \u0111\u1ed1i ch\u1ee9ng v\u00e0 c\u00e1c n\u1ed3ng \u0111\u1ed9 Brev kh\u00e1c nhau cho th\u1ea5y t\u00e1c d\u1ee5ng t\u1ed1t h\u01a1n (H\u00ecnh 3D<\/a>). H\u01a1n n\u1eefa, vi\u1ec7c nhu\u1ed9m c\u00e1c m\u00f4 tim b\u1ec7nh l\u00fd sau c\u00e1c ph\u01b0\u01a1ng ph\u00e1p \u0111i\u1ec1u tr\u1ecb kh\u00e1c nhau cho th\u1ea5y c\u1ea5u tr\u00fac m\u00f4 tim \u1edf chu\u1ed9t trong nh\u00f3m \u0111\u1ed1i ch\u1ee9ng l\u00e0 b\u00ecnh th\u01b0\u1eddng. Kh\u00f4ng gi\u1ed1ng nh\u01b0 nh\u1eefng con trong nh\u00f3m \u0111\u1ed1i ch\u1ee9ng, chu\u1ed9t trong nh\u00f3m Dox bi\u1ec3u hi\u1ec7n m\u1ed9t s\u1ed1 l\u01b0\u1ee3ng l\u1edbn c\u00e1c t\u1ed5n th\u01b0\u01a1ng tim, bao g\u1ed3m ho\u1ea1i t\u1eed, ph\u00f9 n\u1ed9i b\u00e0o, r\u1ed1i lo\u1ea1n v\u00e0 \u0111\u1ee9t s\u1ee3i c\u01a1, c\u0169ng nh\u01b0 tho\u00e1i h\u00f3a d\u1ea1ng s\u00f3ng c\u1ee7a s\u1ee3i tim. \u0110i\u1ec1u th\u00fa v\u1ecb l\u00e0, vi\u1ec7c chu\u1ea9n b\u1ecb tr\u01b0\u1edbc b\u1eb1ng breviscapine \u0111\u00e3 ng\u0103n ng\u1eeba \u0111\u01b0\u1ee3c lo\u1ea1i t\u1ed5n th\u01b0\u01a1ng n\u00e0y, l\u00e0m gi\u1ea3m s\u1ef1 t\u00edch t\u1ee5 qu\u00e1 m\u1ee9c c\u1ee7a lipid \u1edf tim v\u00e0 ph\u1ee5c h\u1ed3i c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i c\u01a1 tim (H\u00ecnh 3F<\/a>). Nhu\u1ed9m kh\u1ed1i c\u01a1 tim cho th\u1ea5y t\u00ecnh tr\u1ea1ng x\u01a1 h\u00f3a m\u00f4 k\u1ebd t\u0103ng l\u00ean \u0111\u00e1ng k\u1ec3 sau khi \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox v\u00e0 s\u1ef1 can thi\u1ec7p c\u1ee7a Brev \u0111\u00e3 l\u00e0m gi\u1ea3m m\u1ee9c \u0111\u1ed9 x\u01a1 h\u00f3a tim (H\u00ecnh 3E<\/a>). D\u1eef li\u1ec7u si\u00eau \u00e2m tim cho th\u1ea5y LVESV v\u00e0 LVID \u1edf nh\u00f3m Dox cao h\u01a1n \u0111\u00e1ng k\u1ec3 so v\u1edbi nh\u00f3m \u0111\u1ed1i ch\u1ee9ng, cho th\u1ea5y s\u1ef1 m\u1edf r\u1ed9ng \u0111\u01b0\u1eddng k\u00ednh khoang t\u00e2m th\u1ea5t v\u00e0 \u0111i\u1ec1u tr\u1ecb b\u1eb1ng breviscapine c\u00f3 th\u1ec3 l\u00e0m gi\u1ea3m \u0111\u00e1ng k\u1ec3 nh\u1eefng thay \u0111\u1ed5i n\u00e0y. Nh\u1eefng k\u1ebft qu\u1ea3 n\u00e0y cho th\u1ea5y breviscapine c\u00f3 th\u1ec3 \u0111\u1ecbnh h\u00ecnh l\u1ea1i qu\u00e1 tr\u00ecnh trao \u0111\u1ed5i ch\u1ea5t c\u1ee7a tim, t\u0103ng s\u1ef1 h\u1ea5p thu glucose c\u1ee7a tim, gi\u1ea3m t\u00ecnh tr\u1ea1ng nhi\u1ec5m m\u1ee1 \u1edf tim v\u00e0 l\u00e0m gi\u1ea3m r\u1ed1i lo\u1ea1n ch\u1ee9c n\u0103ng tim do doxorubicin g\u00e2y ra v\u00e0 nh\u1eefng thay \u0111\u1ed5i v\u1ec1 h\u00ecnh th\u00e1i c\u01a1 tim.<\/p>\n

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\"An<\/a><\/div>\n

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H\u00ccNH 3<\/a><\/div>\n
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(M\u1ed8T)<\/strong>\u00a0S\u01a1 \u0111\u1ed3 \u0111i\u1ec1u tr\u1ecb chu\u1ed9t.\u00a0(B)<\/strong>\u00a018<\/sup>H\u00ecnh \u1ea3nh F-FDG PET\/CT \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n b\u1eb1ng chu\u1ed9t 1 tu\u1ea7n sau l\u1ea7n ti\u1ebfp x\u00fac v\u1edbi Dox \u0111\u1ea7u ti\u00ean v\u00e0 n\u1ed3ng \u0111\u1ed9 18F-FDG \u0111\u01b0\u1ee3c tim h\u1ea5p th\u1ee5.\u00a0(C)<\/strong>\u00a0Si\u00eau \u00e2m tim cho th\u1ea5y breviscapine ng\u0103n ch\u1eb7n s\u1ef1 gi\u00e3n n\u1edf t\u00e2m th\u1ea5t tr\u00e1i do Dox g\u00e2y ra. Si\u00eau \u00e2m tim tr\u1ee5c ng\u1eafn ch\u1ebf \u0111\u1ed9 M \u0111\u1ea1i di\u1ec7n cho th\u1ea5y Dox g\u00e2y ra s\u1ef1 gi\u00e3n n\u1edf t\u00e2m th\u1ea5t tr\u00e1i v\u00e0 breviscapine c\u00f3 t\u00e1c d\u1ee5ng b\u1ea3o v\u1ec7 trong nh\u00f3m Dox + Brev. EF v\u00e0 FS trong t\u00e2m tr\u01b0\u01a1ng th\u1ea5p h\u01a1n \u0111\u00e1ng k\u1ec3 \u1edf nh\u1eefng con chu\u1ed9t \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng breviscapine so v\u1edbi nh\u1eefng con \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox v\u00e0 HR cao h\u01a1n \u0111\u00e1ng k\u1ec3.\u00a0(D)<\/strong>\u00a0Breviscapine l\u00e0m gi\u1ea3m n\u1ed3ng \u0111\u1ed9 cTnI.\u00a0(E)<\/strong>\u00a0Nhu\u1ed9m Masson cho th\u1ea5y breviscapine l\u00e0m gi\u1ea3m m\u1ee9c \u0111\u1ed9 x\u01a1 h\u00f3a tim do Dox g\u00e2y ra.\u00a0(F)<\/strong>\u00a0Nhu\u1ed9m HE cho th\u1ea5y breviscapine b\u1ea3o v\u1ec7 ch\u1ed1ng l\u1ea1i s\u1ef1 gi\u1ea3m k\u00edch th\u01b0\u1edbc t\u1ebf b\u00e0o c\u01a1 tim do Dox g\u00e2y ra trong tim. Ki\u1ec3m so\u00e1t so v\u1edbi Dox, 4 mg\/kg, 8 mg\/kg ho\u1eb7c 16 mg\/kg Brev so v\u1edbi Dox v\u00e0 Dexra so v\u1edbi Dox: ***P<\/em>\u00a0< 0,0005, **P<\/em>\u00a0< 0,005, *P<\/em>\u00a0< 0,05, trung b\u00ecnh \u00b1 SD.\u00a0N<\/em>\u00a0= 6\u20139.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n

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Breviscapine \u0111i\u1ec1u ch\u1ec9nh chuy\u1ec3n h\u00f3a glucose v\u00e0 lipid c\u1ee7a tim b\u1eb1ng c\u00e1ch \u0111i\u1ec1u ch\u1ec9nh n\u1ed3ng \u0111\u1ed9 huy\u1ebft thanh ngo\u1ea1i vi v\u00e0 bi\u1ec3u hi\u1ec7n AKT c\u01a1 tim<\/h3>\n

Ti\u1ebfp theo, ch\u00fang t\u00f4i nghi\u00ean c\u1ee9u c\u00e1ch breviscapine \u0111i\u1ec1u ch\u1ec9nh s\u1ef1 c\u00e2n b\u1eb1ng chuy\u1ec3n h\u00f3a \u0111\u01b0\u1eddng v\u00e0 ch\u1ea5t b\u00e9o. Nh\u01b0 th\u1ec3 hi\u1ec7n trong\u00a0H\u00ecnh 4E<\/a>, m\u1ee9c \u0111\u1ed9 serotonin trong huy\u1ebft thanh ngo\u1ea1i vi \u1edf chu\u1ed9t \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng breviscapine \u0111\u00e3 t\u0103ng \u0111\u00e1ng k\u1ec3 so v\u1edbi \u1edf chu\u1ed9t \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox v\u00e0 m\u1ee9c \u0111\u1ed9 gi\u1ea3m cho th\u1ea5y m\u1ed1i quan h\u1ec7 tuy\u1ebfn t\u00ednh v\u1edbi li\u1ec1u breviscapine, v\u1edbi m\u1ee9c gi\u1ea3m h\u01a1n 95% l\u00e0 quan s\u00e1t th\u1ea5y \u1edf nh\u00f3m d\u00f9ng li\u1ec1u cao. Serotonin (5-HT) l\u00e0 m\u1ed9t monoamine c\u00f3 nhi\u1ec1u ch\u1ee9c n\u0103ng trong h\u1ec7 th\u1ed1ng th\u1ea7n kinh v\u00e0 kh\u00f4ng ph\u1ea3i t\u1ebf b\u00e0o th\u1ea7n kinh (Okaty v\u00e0 c\u1ed9ng s\u1ef1, 2019<\/a>). Trong h\u1ec7 th\u1ed1ng th\u1ea7n kinh trung \u01b0\u01a1ng, 5-HT ho\u1ea1t \u0111\u1ed9ng nh\u01b0 m\u1ed9t ch\u1ea5t d\u1eabn truy\u1ec1n th\u1ea7n kinh \u0111i\u1ec1u ch\u1ec9nh t\u00e2m tr\u1ea1ng v\u00e0 h\u00e0nh vi \u0103n u\u1ed1ng (Berger v\u00e0 c\u1ed9ng s\u1ef1, 2009<\/a>). C\u00e1c nghi\u00ean c\u1ee9u g\u1ea7n \u0111\u00e2y \u0111\u00e3 ch\u1ec9 ra r\u1eb1ng 5-HT ngo\u1ea1i vi \u0111\u00f3ng vai tr\u00f2 quan tr\u1ecdng trong vi\u1ec7c \u0111i\u1ec1u h\u00f2a trao \u0111\u1ed5i ch\u1ea5t c\u1ee7a c\u00e1c m\u00f4 ngo\u1ea1i bi\u00ean b\u1eb1ng c\u00e1ch \u1ee9c ch\u1ebf sinh nhi\u1ec7t th\u00edch nghi \u1edf m\u00f4 m\u1ee1 m\u00e0u n\u00e2u. \u1ee8c ch\u1ebf t\u1ed5ng h\u1ee3p 5-HT l\u00e0m gi\u1ea3m t\u0103ng c\u00e2n v\u00e0 c\u1ea3i thi\u1ec7n r\u1ed1i lo\u1ea1n ch\u1ee9c n\u0103ng trao \u0111\u1ed5i ch\u1ea5t \u1edf m\u00f4 h\u00ecnh chu\u1ed9t b\u00e9o ph\u00ec do ch\u1ebf \u0111\u1ed9 \u0103n ki\u00eang (Zemdegs v\u00e0 c\u1ed9ng s\u1ef1, 2016<\/a>;\u00a0Xia v\u00e0 c\u1ed9ng s\u1ef1, 2021<\/a>). C\u00e1c nghi\u00ean c\u1ee9u li\u00ean k\u1ebft tr\u00ean to\u00e0n b\u1ed9 gen c\u0169ng ti\u1ebft l\u1ed9 m\u1ed1i li\u00ean h\u1ec7 di truy\u1ec1n gi\u1eefa h\u1ec7 th\u1ed1ng serotonergic v\u00e0 b\u00e9o ph\u00ec. Serotonin c\u00f3 hai t\u00e1c d\u1ee5ng kh\u00e1c nhau l\u00ean qu\u00e1 tr\u00ecnh chuy\u1ec3n h\u00f3a glucose: n\u00f3 tr\u1ef1c ti\u1ebfp g\u00e2y ra s\u1ef1 ti\u1ebft insulin trong t\u1ebf b\u00e0o B tuy\u1ebfn t\u1ee5y, l\u00e0m gi\u1ea3m l\u01b0\u1ee3ng \u0111\u01b0\u1eddng trong m\u00e1u; v\u00e0 n\u00f3 \u1ee9c ch\u1ebf s\u1ef1 h\u1ea5p thu glucose t\u1eeb m\u00e1u b\u1edfi c\u00e1c m\u00f4 kh\u00e1c ngo\u00e0i gan v\u00e0 c\u01a1 x\u01b0\u01a1ng, l\u00e0m t\u0103ng l\u01b0\u1ee3ng \u0111\u01b0\u1eddng trong m\u00e1u (Watanabe v\u00e0 c\u1ed9ng s\u1ef1, 2011<\/a>;\u00a0Carmean v\u00e0 c\u1ed9ng s\u1ef1, 2019<\/a>;\u00a0Yabut v\u00e0 c\u1ed9ng s\u1ef1, 2019<\/a>). C\u00e1c nghi\u00ean c\u1ee9u \u0111\u00e3 ch\u1ec9 ra r\u1eb1ng vi\u1ec7c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng serotonin c\u00f3 th\u1ec3 d\u1eabn \u0111\u1ebfn s\u1ef1 gia t\u0103ng \u0111\u1ed9t ng\u1ed9t v\u00e0 l\u1edbn l\u01b0\u1ee3ng \u0111\u01b0\u1eddng trong m\u00e1u, nh\u01b0ng l\u00e0m th\u1ebf n\u00e0o serotonin \u1ee9c ch\u1ebf s\u1ef1 h\u1ea5p thu glucose c\u1ee7a m\u00f4 t\u1eeb m\u00e1u v\u1eabn ch\u01b0a r\u00f5 r\u00e0ng. K\u1ebft qu\u1ea3 th\u1eed nghi\u1ec7m c\u1ee7a ch\u00fang t\u00f4i cho th\u1ea5y sau khi \u0111i\u1ec1u tr\u1ecb b\u1eb1ng breviscapine, n\u1ed3ng \u0111\u1ed9 serotonin ngo\u1ea1i vi gi\u1ea3m m\u1ea1nh, t\u01b0\u01a1ng \u1ee9ng v\u1edbi vi\u1ec7c t\u0103ng l\u01b0\u1ee3ng glucose v\u00e0o tim (H\u00ecnh 4E<\/a>), trong khi l\u01b0\u1ee3ng glucose \u1edf gan kh\u00f4ng thay \u0111\u1ed5i \u0111\u00e1ng k\u1ec3 (H\u00ecnh b\u1ed5 sung S2<\/a>) v\u00e0 m\u1ee9c \u0111\u01b0\u1eddng huy\u1ebft l\u00fac \u0111\u00f3i (FBG) \u0111\u00e3 gi\u1ea3m (H\u00ecnh 4A<\/a>). Trong nh\u00f3m breviscapine, vi\u1ec7c b\u1ed5 sung th\u00eam 5-HT l\u00e0m t\u0103ng m\u1ee9c \u0111\u1ed9 serotonin \u1edf chu\u1ed9t v\u00e0 gi\u1ea3m s\u1ef1 h\u1ea5p thu glucose \u1edf tim (H\u00ecnh 4B<\/a>). \u0110\u1ec3 ph\u00e2n t\u00edch s\u00e2u h\u01a1n v\u1ec1 c\u00e1ch serotonin \u0111i\u1ec1u ch\u1ec9nh qu\u00e1 tr\u00ecnh chuy\u1ec3n h\u00f3a t\u1ebf b\u00e0o c\u01a1 tim, ch\u00fang t\u00f4i \u0111\u00e3 b\u1ed5 sung th\u00eam 5-HT \u0111\u1ec3 t\u0103ng m\u1ee9c serotonin \u1edf chu\u1ed9t m\u00f4 h\u00ecnh ch\u1ea5n th\u01b0\u01a1ng c\u01a1 tim do Dox g\u00e2y ra v\u00e0 sau \u0111\u00f3 thu th\u1eadp tim c\u1ee7a chu\u1ed9t \u0111\u1ec3 ph\u00e2n t\u00edch phi\u00ean m\u00e3. K\u1ebft qu\u1ea3 cho th\u1ea5y qu\u00e1 tr\u00ecnh oxy h\u00f3a axit b\u00e9o \u1edf nh\u00f3m \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox v\u00e0 5-HT cao h\u01a1n \u0111\u00e1ng k\u1ec3 so v\u1edbi ch\u1ec9 ri\u00eang nh\u00f3m Dox (H\u00ecnh b\u1ed5 sung S3<\/a>). Sau \u0111\u00f3, ch\u00fang t\u00f4i \u0111\u00e3 ph\u00e2n t\u00edch nh\u1eefng thay \u0111\u1ed5i trong con \u0111\u01b0\u1eddng PI3K-protein kinase B (Akt\/PKB), m\u1ed9t ch\u1ea5t \u0111i\u1ec1u h\u00f2a quan tr\u1ecdng trong qu\u00e1 tr\u00ecnh chuy\u1ec3n h\u00f3a glucose \u1edf c\u01a1 tim c\u00f3 vai tr\u00f2 quan tr\u1ecdng trong vi\u1ec7c \u0111i\u1ec1u ch\u1ec9nh s\u1ef1 h\u1ea5p thu glucose; th\u00fac \u0111\u1ea9y s\u1ef1 ph\u00e2n chia, t\u0103ng sinh v\u00e0 s\u1ed1ng s\u00f3t c\u1ee7a t\u1ebf b\u00e0o; v\u00e0 \u1ee9c ch\u1ebf apoptosis. K\u1ebft qu\u1ea3 cho th\u1ea5y vi\u1ec7c b\u1ed5 sung 5-HT \u1ee9c ch\u1ebf tr\u1ef1c ti\u1ebfp s\u1ef1 bi\u1ec3u hi\u1ec7n gen c\u1ee7a Akt nh\u01b0ng kh\u00f4ng l\u00e0m thay \u0111\u1ed5i \u0111\u00e1ng k\u1ec3 m\u1ee9c \u0111\u1ed9 ti\u1ec3u \u0111\u01a1n v\u1ecb x\u00fac t\u00e1c PI3K ho\u1eb7c ti\u1ec3u \u0111\u01a1n v\u1ecb \u0111i\u1ec1u h\u00f2a (H\u00ecnh 4C<\/a>). M\u1ea5t AKT l\u00e0m gi\u1ea3m kh\u1ea3 n\u0103ng chuy\u1ec3n h\u00f3a glucose c\u1ee7a t\u1ebf b\u00e0o c\u01a1 tim. Nh\u1eefng k\u1ebft qu\u1ea3 n\u00e0y cho th\u1ea5y breviscapine l\u00e0m gi\u1ea3m t\u00e1c d\u1ee5ng \u1ee9c ch\u1ebf c\u1ee7a serotonin \u0111\u1ed1i v\u1edbi s\u1ef1 h\u1ea5p thu glucose c\u1ee7a m\u00f4 b\u1eb1ng c\u00e1ch gi\u1ea3m \u0111\u00e1ng k\u1ec3 m\u1ee9c \u0111\u1ed9 serotonin v\u00e0 \u0111\u1ea3m b\u1ea3o s\u1ef1 h\u1ea5p thu glucose t\u1eeb m\u00e1u trong \u0111i\u1ec1u ki\u1ec7n b\u1ec7nh l\u00fd, cho th\u1ea5y kh\u1ea3 n\u0103ng c\u01a1 th\u1ec3 c\u00f3 th\u1ec3 tham gia v\u00e0o qu\u00e1 tr\u00ecnh \u0111i\u1ec1u h\u00f2a chuy\u1ec3n h\u00f3a c\u1ee7a tim. t\u00e1i c\u1ea5u tr\u00fac th\u00f4ng qua c\u00e1c ch\u1ea5t d\u1eabn truy\u1ec1n th\u1ea7n kinh. Quan tr\u1ecdng h\u01a1n, breviscapine, m\u1ed9t lo\u1ea1i thu\u1ed1c tim m\u1ea1ch \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng ph\u1ed5 bi\u1ebfn \u1edf Trung Qu\u1ed1c, c\u00f3 th\u1ec3 l\u00e0m gi\u1ea3m n\u1ed3ng \u0111\u1ed9 serotonin ngo\u1ea1i bi\u00ean h\u01a1n 90% v\u00e0 c\u00f3 t\u00e1c d\u1ee5ng m\u1ea1nh h\u01a1n thu\u1ed1c \u1ee9c ch\u1ebf t\u00e1i h\u1ea5p thu serotonin c\u1ed5 \u0111i\u1ec3n fluoxetine trong \u0111i\u1ec1u tr\u1ecb ph\u00ec \u0111\u1ea1i c\u01a1 tim v\u00e0 suy tim do chuy\u1ec3n h\u00f3a glucose c\u01a1 tim. r\u1ed1i lo\u1ea1n v\u00e0 ti\u1ec3u \u0111\u01b0\u1eddng, \u0111\u1ea1i di\u1ec7n cho m\u1ed9t t\u00e1c nh\u00e2n an to\u00e0n m\u1edbi \u0111\u1ec3 \u0111i\u1ec1u tr\u1ecb nhi\u1ec5m \u0111\u1ed9c tim do Dox g\u00e2y ra. C\u00e1c nghi\u00ean c\u1ee9u d\u1ecbch t\u1ec5 h\u1ecdc c\u0169ng ch\u1ec9 ra r\u1eb1ng b\u1ec7nh ti\u1ec3u \u0111\u01b0\u1eddng l\u00e0m t\u0103ng nguy c\u01a1 nhi\u1ec5m \u0111\u1ed9c tim do Dox g\u00e2y ra; do \u0111\u00f3, nghi\u00ean c\u1ee9u n\u00e0y cung c\u1ea5p m\u1ed9t chi\u1ebfn l\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb ti\u1ec1m n\u0103ng cho b\u1ec7nh nh\u00e2n ti\u1ec3u \u0111\u01b0\u1eddng v\u00e0 ung th\u01b0 (Chang v\u00e0 c\u1ed9ng s\u1ef1, 2021<\/a>).<\/p>\n

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\"An<\/a><\/div>\n

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HINH 4<\/a><\/div>\n
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(M\u1ed8T)<\/strong>\u00a0M\u1ee9c \u0111\u01b0\u1eddng huy\u1ebft l\u00fac \u0111\u00f3i \u1edf chu\u1ed9t.\u00a0(B)<\/strong>\u00a0N\u1ed3ng \u0111\u1ed9 c\u1ee7a\u00a018<\/sup>F-FDG \u0111\u01b0\u1ee3c tim h\u1ea5p th\u1ee5 sau khi b\u1ed5 sung 5-HT.\u00a0(C)<\/strong>\u00a0B\u1ea3n \u0111\u1ed3 nhi\u1ec7t c\u1ee7a ph\u00e2n t\u00edch b\u1ea3ng \u0111i\u1ec3m sau khi b\u1ed5 sung 5-HT.\u00a0(D)<\/strong>\u00a0M\u1ee9c bi\u1ec3u hi\u1ec7n c\u1ee7a PI3K, Akt v\u00e0 GAPDH \u0111\u00e3 \u0111\u01b0\u1ee3c \u0111o\u00a0trong \u1ed1ng nghi\u1ec7m<\/em>\u00a0c\u1ee7a WB.\u00a0(E)<\/strong>\u00a0M\u1ee9c \u0111\u1ed9 serotonin trong huy\u1ebft thanh ngo\u1ea1i vi \u1edf chu\u1ed9t.\u00a0(F)<\/strong>\u00a0M\u1ee9c \u0111\u1ed9 D-glucose 6-phosphate \u1edf chu\u1ed9t.\u00a0(G)<\/strong>\u00a0M\u1ee9c \u0111\u1ed9 axit \u03b1-ketoglutaric \u1edf chu\u1ed9t. Ki\u1ec3m so\u00e1t so v\u1edbi Dox, 4 mg\/kg, 8 mg\/kg ho\u1eb7c 16 mg\/kg Brev so v\u1edbi Dox v\u00e0 Brev+5-HT so v\u1edbi Brev: ***P<\/em>\u00a0< 0,0005, **P<\/em>\u00a0< 0,005, *P<\/em>\u00a0< 0,05, trung b\u00ecnh \u00b1 SD.\u00a0N<\/em>\u00a0= 6\u20139.<\/p>\n<\/div>\n<\/div>\n<\/div>\n

D\u1ef1a tr\u00ean nh\u1eefng ph\u00e1t hi\u1ec7n n\u00e0y, ch\u00fang t\u00f4i \u0111\u00e3 nghi\u00ean c\u1ee9u c\u00e1ch breviscapine \u0111i\u1ec1u ch\u1ec9nh glucose. S\u1eed d\u1ee5ng b\u1eb1ng tr\u00e1i tim. K\u1ebft qu\u1ea3 cho th\u1ea5y bi\u1ec3u hi\u1ec7n protein PI3K \u1edf chu\u1ed9t ti\u1ebfp x\u00fac v\u1edbi Dox \u0111\u00e3 gi\u1ea3m \u0111\u00e1ng k\u1ec3 v\u00e0 m\u1ee9c \u0111\u1ed9 bi\u1ec3u hi\u1ec7n protein PI3K trong m\u00f4 tim \u0111\u00e3 t\u0103ng l\u00ean \u0111\u00e1ng k\u1ec3 sau khi can thi\u1ec7p b\u1eb1ng breviscapine. \u0110i\u1ec1u th\u00fa v\u1ecb l\u00e0, bi\u1ec3u hi\u1ec7n AKT \u0111\u01b0\u1ee3c duy tr\u00ec \u1edf m\u1ee9c th\u1ea5p \u1edf c\u1ea3 nh\u00f3m \u0111\u1ed1i ch\u1ee9ng v\u00e0 nh\u00f3m ti\u1ebfp x\u00fac v\u1edbi Dox, v\u00e0 bi\u1ec3u hi\u1ec7n AKT t\u0103ng \u0111\u00e1ng k\u1ec3 \u0111\u00e3 \u0111\u01b0\u1ee3c quan s\u00e1t th\u1ea5y sau khi \u0111i\u1ec1u tr\u1ecb b\u1eb1ng breviscapine (H\u00ecnh 4D<\/a>). C\u00e1c nghi\u00ean c\u1ee9u tr\u01b0\u1edbc \u0111\u00e2y cho th\u1ea5y AKT k\u00edch th\u00edch chuy\u1ec3n h\u00f3a glucose trong t\u1ebf b\u00e0o, chuy\u1ec3n glucose th\u00e0nh D-glucose 6-phosphate\u00a0th\u00f4ng qua<\/em>\u00a0hexokinase \u0111\u1ec3 ph\u00e2n gi\u1ea3i \u0111\u01b0\u1eddng ph\u00e2n ho\u1eb7c tr\u00f9ng h\u1ee3p th\u00e0nh glycogen. K\u1ebft qu\u1ea3 c\u1ee7a ch\u00fang t\u00f4i cho th\u1ea5y r\u1eb1ng sau khi breviscapine th\u00fac \u0111\u1ea9y bi\u1ec3u hi\u1ec7n AKT c\u01a1 tim, n\u1ed3ng \u0111\u1ed9 D-glucose 6-phosphate v\u00e0 axit \u03b1-ketoglutaric li\u00ean quan \u0111\u1ebfn chuy\u1ec3n h\u00f3a glucose \u0111\u00e3 t\u0103ng l\u00ean \u0111\u00e1ng k\u1ec3 (H\u00ecnh 4F<\/a>,G), cho th\u1ea5y r\u1eb1ng breviscapine \u0111\u00e3 t\u0103ng c\u01b0\u1eddng kh\u1ea3 n\u0103ng s\u1eed d\u1ee5ng glucose c\u1ee7a c\u01a1 tim l\u00e0m ngu\u1ed3n n\u0103ng l\u01b0\u1ee3ng th\u00f4ng qua AKT v\u00e0 th\u00fac \u0111\u1ea9y qu\u00e1 tr\u00ecnh d\u1ecb h\u00f3a glucose. C\u00e1c nghi\u00ean c\u1ee9u tr\u01b0\u1edbc \u0111\u00e2y \u0111\u00e3 b\u00e1o c\u00e1o r\u1eb1ng bi\u1ec3u hi\u1ec7n PI3K-Akt t\u0103ng l\u00ean c\u00f3 th\u1ec3 th\u00fac \u0111\u1ea9y vi\u1ec7c s\u1eed d\u1ee5ng \u0111\u01b0\u1eddng \u1edf c\u00e1c m\u00f4 ngo\u1ea1i bi\u00ean, gi\u1ea3m t\u00ecnh tr\u1ea1ng kh\u00e1ng insulin, t\u0103ng c\u01b0\u1eddng cung c\u1ea5p n\u0103ng l\u01b0\u1ee3ng cho tim v\u00e0 ng\u0103n ng\u1eeba suy tim, trong khi vi\u1ec7c \u1ee9c ch\u1ebf con \u0111\u01b0\u1eddng PI3K-Akt \u1ea3nh h\u01b0\u1edfng \u0111\u1ebfn ho\u1ea1t \u0111\u1ed9ng sinh l\u00fd c\u1ee7a t\u1ebf b\u00e0o tim (Zhu v\u00e0 c\u1ed9ng s\u1ef1, 2013<\/a>). Nh\u1eefng k\u1ebft qu\u1ea3 n\u00e0y cho th\u1ea5y breviscapine t\u0103ng c\u01b0\u1eddng kh\u1ea3 n\u0103ng ch\u1ed1ng l\u1ea1i t\u1ed5n th\u01b0\u01a1ng c\u01a1 tim do Dox g\u00e2y ra b\u1eb1ng c\u00e1ch \u0111i\u1ec1u ch\u1ec9nh k\u00edch ho\u1ea1t con \u0111\u01b0\u1eddng PI3K-Akt. Nh\u1eefng k\u1ebft qu\u1ea3 n\u00e0y cho th\u1ea5y breviscapine \u0111i\u1ec1u ch\u1ec9nh l\u01b0\u1ee3ng \u0111\u01b0\u1eddng trong m\u00e1u b\u1eb1ng c\u00e1ch \u1ee9c ch\u1ebf serotonin, ng\u0103n ch\u1eb7n vi\u1ec7c h\u1ea1n ch\u1ebf s\u1eed d\u1ee5ng glucose trong c\u01a1 tim v\u00e0 th\u00fac \u0111\u1ea9y chuy\u1ec3n h\u00f3a glucose trong c\u01a1 tim b\u1eb1ng c\u00e1ch k\u00edch ho\u1ea1t con \u0111\u01b0\u1eddng PI3K-Akt. Do \u0111\u00f3, serotonin c\u00f3 th\u1ec3 l\u00e0 m\u1ee5c ti\u00eau quan tr\u1ecdng \u0111\u1ec3 \u0111i\u1ec1u ch\u1ec9nh chuy\u1ec3n h\u00f3a glycolipid c\u1ee7a tim. Sau \u0111\u00f3, ch\u00fang t\u00f4i \u0111\u00e3 ph\u00e2n t\u00edch nh\u1eefng thay \u0111\u1ed5i trong ch\u1ee9c n\u0103ng tim v\u00e0 c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i sau khi t\u00e1i c\u1ea5u tr\u00fac qu\u00e1 tr\u00ecnh chuy\u1ec3n h\u00f3a glycolipid c\u1ee7a c\u01a1 tim. So v\u1edbi nh\u00f3m m\u00f4 h\u00ecnh Dox, s\u1ea3n xu\u1ea5t ATP c\u1ee7a c\u01a1 tim \u1edf nh\u00f3m \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng breviscapine \u0111\u00e3 t\u0103ng \u0111\u00e1ng k\u1ec3 (H\u00ecnh 5A<\/a>), trong khi h\u00e0m l\u01b0\u1ee3ng ROS v\u00e0 MDA, m\u1ed9t ch\u1ea5t chuy\u1ec3n h\u00f3a c\u1ee7a FAO, l\u1ea1i gi\u1ea3m \u0111\u00e1ng k\u1ec3 (H\u00ecnh 5B,E<\/a>). Ph\u00e2n t\u00edch chuy\u1ec3n h\u00f3a n\u0103ng l\u01b0\u1ee3ng O2K cho th\u1ea5y breviscapine \u1ee9c ch\u1ebf s\u1ef1 gia t\u0103ng \u0111\u00e1ng k\u1ec3 m\u1ee9c ti\u00eau th\u1ee5 oxy c\u1ee7a tim do ti\u1ebfp x\u00fac v\u1edbi Dox (H\u00ecnh 5C<\/a>), l\u00e0m gi\u1ea3m \u0111\u00e1ng k\u1ec3 t\u1ef7 l\u1ec7 s\u1ea3n xu\u1ea5t ATP\/ti\u00eau th\u1ee5 oxy (H\u00ecnh 5D<\/a>) v\u00e0 b\u00ecnh th\u01b0\u1eddng h\u00f3a ti\u1ec1m n\u0103ng m\u00e0ng ty th\u1ec3 (H\u00ecnh b\u1ed5 sung S4<\/a>). \u0110i\u1ec1u n\u00e0y cho th\u1ea5y r\u1eb1ng \u0111i\u1ec1u tr\u1ecb b\u1eb1ng breviscapine l\u00e0m t\u0103ng kh\u1ea3 n\u0103ng s\u1eed d\u1ee5ng glucose hi\u1ec7u qu\u1ea3 n\u0103ng l\u01b0\u1ee3ng cao c\u1ee7a c\u01a1 tim l\u00e0m ngu\u1ed3n n\u0103ng l\u01b0\u1ee3ng; c\u1ea3i thi\u1ec7n hi\u1ec7u qu\u1ea3 s\u1ea3n xu\u1ea5t ATP; v\u00e0 gi\u1ea3m t\u1ea3i cho tim, stress oxy h\u00f3a v\u00e0 ti\u00eau th\u1ee5 oxy c\u1ee7a c\u01a1 tim. T\u00f3m l\u1ea1i, breviscapine c\u00f3 th\u1ec3 ph\u00e1 v\u1ee1 v\u00f2ng lu\u1ea9n qu\u1ea9n c\u1ee7a t\u1ed1c \u0111\u1ed9 ti\u00eau th\u1ee5 oxy cao v\u00e0 qu\u00e1 tr\u00ecnh \u0111\u1ed1t ch\u00e1y lipid kh\u00f4ng \u0111\u1ee7 trong tim do ti\u1ebfp x\u00fac v\u1edbi Dox m\u1ed9t c\u00e1ch hi\u1ec7u qu\u1ea3 b\u1eb1ng c\u00e1ch \u0111i\u1ec1u ch\u1ec9nh v\u00f2ng AKT serotonin-glycemia-c\u01a1 tim, t\u00e1i c\u1ea5u tr\u00fac chuy\u1ec3n h\u00f3a n\u0103ng l\u01b0\u1ee3ng c\u1ee7a c\u01a1 tim, t\u0103ng s\u1eed d\u1ee5ng glucose v\u00e0 gi\u1ea3m FAO. (H\u00ecnh 5F<\/a>), ng\u0103n c\u1ea3n s\u1ef1 ph\u00e1t tri\u1ec3n h\u01a1n n\u1eefa c\u1ee7a DIC.<\/p>\n

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\"An<\/a><\/div>\n

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H\u00ccNH 5<\/a><\/div>\n
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(M\u1ed8T)<\/strong>\u00a0H\u00e0m l\u01b0\u1ee3ng ATP trong c\u00e1c t\u1ebf b\u00e0o H9c2.\u00a0(B)<\/strong>\u00a0N\u1ed9i dung MDA trong c\u00e1c \u00f4 H9c2.\u00a0(C)<\/strong>\u00a0Ti\u00eau th\u1ee5 oxy c\u1ee7a tim trong c\u00e1c t\u1ebf b\u00e0o H9c2.\u00a0(D)<\/strong>\u00a0T\u1ef7 l\u1ec7 s\u1ea3n xu\u1ea5t\/ti\u00eau th\u1ee5 oxy c\u1ee7a ATP trong t\u1ebf b\u00e0o H9c2.\u00a0(E)<\/strong>\u00a0C\u01b0\u1eddng \u0111\u1ed9 nhu\u1ed9m ROS trong c\u00e1c t\u1ebf b\u00e0o H9c2.\u00a0(F)<\/strong>\u00a0S\u01a1 \u0111\u1ed3. Ki\u1ec3m so\u00e1t so v\u1edbi Dox, Brev so v\u1edbi Dox v\u00e0 Dexra so v\u1edbi Dox: ***P<\/em>\u00a0< 0,0005, **P<\/em>\u00a0< 0,005, *P<\/em>\u00a0< 0,05, trung b\u00ecnh \u00b1 SD.\u00a0N<\/em>\u00a0= 6\u20139.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n

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Breviscapine l\u00e0m s\u1ea1ch t\u1ed5n th\u01b0\u01a1ng ty th\u1ec3 v\u00e0 ph\u1ee5c h\u1ed3i c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i c\u01a1 tim sau khi \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox th\u00f4ng qua con \u0111\u01b0\u1eddng truy\u1ec1n t\u00edn hi\u1ec7u PINK1\/Parkin<\/h3>\n

M\u1eb7c d\u00f9 c\u00e1c gi\u1ea3 thuy\u1ebft li\u00ean quan \u0111\u1ebfn c\u01a1 ch\u1ebf c\u1ee7a DIC \u0111\u00e3 thay \u0111\u1ed5i trong nhi\u1ec1u th\u1eadp k\u1ef7 qua, nh\u01b0ng \u0111\u1eb7c \u0111i\u1ec3m ch\u00ednh c\u1ee7a DIC l\u00e0 m\u1ea5t c\u00e2n b\u1eb1ng oxy h\u00f3a kh\u1eed v\u00e0 suy gi\u1ea3m ch\u1ee9c n\u0103ng ty th\u1ec3. C\u00e1c k\u1ebft qu\u1ea3 tr\u01b0\u1edbc \u0111\u00e2y \u0111\u00e3 ng\u0103n c\u1ea3n vi\u1ec7c c\u1ea3i thi\u1ec7n gi\u1ea3 thuy\u1ebft v\u1ec1 s\u1ef1 ph\u00e1t tri\u1ec3n DIC t\u1eeb g\u00f3c \u0111\u1ed9 t\u1ef7 l\u1ec7 n\u0103ng l\u01b0\u1ee3ng c\u1ee7a tim v\u00e0 hi\u1ec7u qu\u1ea3 s\u1ea3n xu\u1ea5t n\u0103ng l\u01b0\u1ee3ng nh\u01b0ng \u0111\u1eb7t ra m\u1ed9t c\u00e2u h\u1ecfi quan tr\u1ecdng, \u0111\u00f3 l\u00e0 l\u00e0m th\u1ebf n\u00e0o breviscapine \u0111\u1ea1t \u0111\u01b0\u1ee3c hi\u1ec7u qu\u1ea3 s\u1ea3n xu\u1ea5t n\u0103ng l\u01b0\u1ee3ng v\u00e0 c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i vi m\u00f4i tr\u01b0\u1eddng tim b\u1eb1ng c\u00e1ch t\u1ed1i \u01b0u h\u00f3a m\u1ea1ng l\u01b0\u1edbi chuy\u1ec3n h\u00f3a trong tim sau ty th\u1ec3. ch\u1ea5n th\u01b0\u01a1ng. V\u00ec v\u1eady, ch\u00fang t\u00f4i nh\u1eb1m m\u1ee5c \u0111\u00edch tr\u1ea3 l\u1eddi c\u00e2u h\u1ecfi n\u00e0y. Con \u0111\u01b0\u1eddng truy\u1ec1n t\u00edn hi\u1ec7u kinase1 PINK1\/Parkin gi\u1ea3 \u0111\u1ecbnh do Pten g\u00e2y ra l\u00e0 m\u1ed9t trong nh\u1eefng con \u0111\u01b0\u1eddng ch\u00ednh \u0111\u01b0\u1ee3c trung gian b\u1edfi s\u1ef1 t\u1ef1 th\u1ef1c c\u1ee7a ty th\u1ec3 v\u00e0 \u0111\u00f3ng vai tr\u00f2 quan tr\u1ecdng trong vi\u1ec7c duy tr\u00ec qu\u00e1 tr\u00ecnh chuy\u1ec3n h\u00f3a n\u0103ng l\u01b0\u1ee3ng c\u1ee7a t\u1ebf b\u00e0o c\u01a1 tim (Dewanjee v\u00e0 c\u1ed9ng s\u1ef1, 2021<\/a>). Khi ty th\u1ec3 trong t\u1ebf b\u00e0o c\u01a1 tim b\u1ecb t\u1ed5n th\u01b0\u01a1ng, PINK1, v\u1edbi t\u01b0 c\u00e1ch l\u00e0 \u201cng\u01b0\u1eddi canh g\u00e1c\u201d c\u1ee7a h\u1ec7 th\u1ed1ng ki\u1ec3m so\u00e1t ch\u1ea5t l\u01b0\u1ee3ng ty th\u1ec3, s\u1ebd t\u00edch t\u1ee5 \u1edf m\u00e0ng ngo\u00e0i c\u1ee7a ty th\u1ec3 v\u00e0 thu th\u1eadp v\u00e0 phosphoryl h\u00f3a Parkin (Poole v\u00e0 Macleod, 2021<\/a>). Parkin \u0111\u01b0\u1ee3c k\u00edch ho\u1ea1t s\u1ebd ph\u1ed5 bi\u1ebfn c\u00e1c ty th\u1ec3 b\u1ecb t\u1ed5n th\u01b0\u01a1ng, sau \u0111\u00f3 h\u1ee3p nh\u1ea5t v\u1edbi lysosome \u0111\u1ec3 tho\u00e1i h\u00f3a ho\u00e0n to\u00e0n. Qu\u00e1 tr\u00ecnh t\u1ef1 th\u1ef1c b\u00e0o c\u1ee7a ty th\u1ec3 \u0111\u01b0\u1ee3c t\u0103ng c\u01b0\u1eddng qua trung gian con \u0111\u01b0\u1eddng truy\u1ec1n t\u00edn hi\u1ec7u PINK1\/Parkin c\u00f3 th\u1ec3 duy tr\u00ec c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i c\u1ee7a ty th\u1ec3 trong t\u1ebf b\u00e0o c\u01a1 tim v\u00e0 l\u00e0m ch\u1eadm s\u1ef1 ti\u1ebfn tri\u1ec3n c\u1ee7a b\u1ec7nh tim (Dorn, 2016<\/a>).<\/p>\n

Do \u0111\u00f3, ch\u00fang t\u00f4i \u0111\u00e3 suy \u0111o\u00e1n r\u1eb1ng breviscapine t\u0103ng c\u01b0\u1eddng kh\u1ea3 n\u0103ng t\u1ef1 th\u1ef1c c\u1ee7a ty th\u1ec3 th\u00f4ng qua con \u0111\u01b0\u1eddng PINK1\/Parkin v\u00e0 duy tr\u00ec c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i c\u1ee7a ty th\u1ec3 trong t\u1ebf b\u00e0o c\u01a1 tim. WB cho th\u1ea5y so v\u1edbi nh\u00f3m Dox, t\u1ed5ng m\u1ee9c bi\u1ec3u hi\u1ec7n protein PINK1\/Parkin \u1edf nh\u00f3m \u0111i\u1ec1u tr\u1ecb b\u1eb1ng breviscapine \u0111\u00e3 t\u0103ng l\u00ean \u0111\u00e1ng k\u1ec3 (H\u00ecnh 6A<\/a>) v\u00e0 m\u1ee9c \u0111\u1ed9 phosphoryl h\u00f3a t\u01b0\u01a1ng \u1ee9ng c\u0169ng t\u0103ng l\u00ean \u0111\u00e1ng k\u1ec3 (H\u00ecnh 6B<\/a>). Trong nh\u00f3m \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox, bi\u1ec3u hi\u1ec7n protein PINK1\/Parkin c\u00f3 xu h\u01b0\u1edbng gi\u1ea3m v\u00e0 qu\u00e1 tr\u00ecnh phosphoryl h\u00f3a protein gi\u1ea3m \u0111\u00e1ng k\u1ec3, trong khi m\u1ee9c \u0111\u1ed9 protein m\u00e0ng ty th\u1ec3 Tom20 t\u0103ng l\u00ean, cho th\u1ea5y r\u1eb1ng m\u1eb7c d\u00f9 Dox g\u00e2y ra t\u1ed5n th\u01b0\u01a1ng ty th\u1ec3 nh\u01b0ng n\u00f3 \u0111\u00e3 \u1ee9c ch\u1ebf qu\u00e1 tr\u00ecnh \u0111\u00e0o th\u1ea3i k\u1ecbp th\u1eddi c\u00e1c t\u1ebf b\u00e0o b\u1ecb h\u01b0 h\u1ecfng. ty th\u1ec3. M\u1ed9t s\u1ed1 l\u01b0\u1ee3ng l\u1edbn ty th\u1ec3 b\u1ecb g\u00e3y v\u00e0 h\u01b0 h\u1ecfng \u0111\u00e3 \u0111\u01b0\u1ee3c quan s\u00e1t th\u1ea5y trong nh\u00f3m Dox (m\u0169i t\u00ean \u0111\u1ecf,\u00a0H\u00ecnh 6D<\/a>), trong khi m\u1ed9t l\u01b0\u1ee3ng l\u1edbn b\u1ec7nh t\u1ef1 k\u1ef7 c\u1ee7a ty th\u1ec3 \u0111\u01b0\u1ee3c b\u1ecdc lysosomal \u0111\u00e3 \u0111\u01b0\u1ee3c quan s\u00e1t th\u1ea5y trong nh\u00f3m Brev (m\u0169i t\u00ean m\u00e0u xanh). Khi Dox v\u00e0 Brev \u0111\u01b0\u1ee3c \u00e1p d\u1ee5ng \u0111\u1ed3ng th\u1eddi, \u0111\u01b0\u1eddng g\u1edd ty th\u1ec3 l\u1ed9 r\u00f5, h\u00ecnh th\u00e1i ty th\u1ec3 b\u00ecnh th\u01b0\u1eddng v\u00e0 c\u1ea5u tr\u00fac m\u00e0ng c\u00f2n nguy\u00ean v\u1eb9n. Khi nhu\u1ed9m b\u1eb1ng MitoTracker, c\u01b0\u1eddng \u0111\u1ed9 hu\u1ef3nh quang cao nh\u1ea5t \u0111\u01b0\u1ee3c t\u00ecm th\u1ea5y \u1edf nh\u00f3m Dox (H\u00ecnh 6C<\/a>), ch\u1ec9 ra r\u1eb1ng c\u00f3 nhi\u1ec1u ty th\u1ec3 h\u01a1n \u0111\u00e1ng k\u1ec3 trong nh\u00f3m Dox so v\u1edbi nh\u00f3m \u0111\u1ed1i ch\u1ee9ng v\u00e0 nh\u00f3m Brev. H\u01a1n n\u1eefa, m\u1ee9c \u0111\u1ed9 protein ch\u1ed1ng oxy h\u00f3a NADH v\u00e0 SOD \u0111\u00e3 t\u0103ng l\u00ean \u0111\u00e1ng k\u1ec3 sau khi \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Brev (H\u00ecnh b\u1ed5 sung S5<\/a>). Qu\u00e1 tr\u00ecnh phosphoryl h\u00f3a c\u1ee7a th\u1ee5 th\u1ec3 n\u0103ng l\u01b0\u1ee3ng AMPK \u0111\u00e3 gi\u1ea3m \u0111\u00e1ng k\u1ec3 \u1edf nh\u00f3m \u0111i\u1ec1u tr\u1ecb Brev so v\u1edbi nh\u00f3m Dox, trong khi c\u00e1c trung t\u00e2m ki\u1ec3m so\u00e1t t\u0103ng tr\u01b0\u1edfng t\u1ebf b\u00e0o \u0111\u01b0\u1ee3c k\u00edch ho\u1ea1t (H\u00ecnh 6E<\/a>). Nh\u1eefng k\u1ebft qu\u1ea3 n\u00e0y ch\u1ec9 ra r\u1eb1ng ph\u01a1i nhi\u1ec5m Dox g\u00e2y t\u1ed5n th\u01b0\u01a1ng c\u01a1 tim, t\u00edch t\u1ee5 ty th\u1ec3 v\u00e0 m\u1ea5t c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i, \u0111i\u1ec1u n\u00e0y gi\u1ea3i th\u00edch \u1edf m\u1ed9t m\u1ee9c \u0111\u1ed9 n\u00e0o \u0111\u00f3 t\u1ea1i sao hi\u1ec7u qu\u1ea3 s\u1ea3n xu\u1ea5t n\u0103ng l\u01b0\u1ee3ng c\u1ee7a tim b\u1ecb gi\u1ea3m v\u00e0 c\u0103ng th\u1eb3ng oxy h\u00f3a t\u0103ng l\u00ean sau khi d\u00f9ng Dox. Breviscapine c\u00f3 th\u1ec3 th\u00fac \u0111\u1ea9y qu\u00e1 tr\u00ecnh t\u1ef1 th\u1ef1c b\u00e0o c\u1ee7a ty th\u1ec3, lo\u1ea1i b\u1ecf ty th\u1ec3 b\u1ecb t\u1ed5n th\u01b0\u01a1ng v\u00e0 kh\u00f4i ph\u1ee5c c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i c\u1ee7a c\u01a1 tim, \u0111\u1ea3m b\u1ea3o hi\u1ec7u qu\u1ea3 s\u1ef1 c\u00e2n b\u1eb1ng \u0111\u1ed9ng gi\u1eefa s\u1ea3n xu\u1ea5t ATP c\u1ee7a tim v\u00e0 stress oxy h\u00f3a.<\/p>\n

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(M\u1ed8T)<\/strong>\u00a0M\u1ee9c \u0111\u1ed9 bi\u1ec3u hi\u1ec7n c\u1ee7a PINK1, Parkin, Tom20 v\u00e0 GAPDH \u0111\u00e3 \u0111\u01b0\u1ee3c \u0111o\u00a0trong \u1ed1ng nghi\u1ec7m<\/em>\u00a0c\u1ee7a WB.\u00a0(B)<\/strong>\u00a0M\u1ee9c \u0111\u1ed9 bi\u1ec3u hi\u1ec7n c\u1ee7a p-PINK1, p-Parkin v\u00e0 Tom20 \u0111\u00e3 \u0111\u01b0\u1ee3c \u0111\u00e1nh gi\u00e1.\u00a0(C)<\/strong>\u00a0Nhu\u1ed9m Mitotracer.\u00a0(D)<\/strong>\u00a0K\u00ednh hi\u1ec3n vi \u0111i\u1ec7n t\u1eed.\u00a0(E)<\/strong>\u00a0C\u00e1c m\u1ee9c bi\u1ec3u hi\u1ec7n c\u1ee7a p-AMPK, p-mTOR, p-Akt v\u00e0 p-PI3K \u0111\u00e3 \u0111\u01b0\u1ee3c \u0111\u00e1nh gi\u00e1.\u00a0(F)<\/strong>\u00a0C\u01b0\u1eddng \u0111\u1ed9 nhu\u1ed9m ROS trong c\u00e1c t\u1ebf b\u00e0o H9c2 sau khi b\u1ed5 sung Mdivi-1.\u00a0(G)<\/strong>\u00a0H\u00e0m l\u01b0\u1ee3ng ATP trong t\u1ebf b\u00e0o H9c2 sau khi b\u1ed5 sung Mdivi-1.(H)<\/strong>\u00a0Bi\u1ec3u \u0111\u1ed3 thanh c\u1ee7a p-AMPK\/t-AMPK, p-mTOR\/t-mTOR, p-Akt\/t-Akt v\u00e0 p-PI3K\/t-PI3K. Ki\u1ec3m so\u00e1t so v\u1edbi Dox, Dox + Mdivi-1 so v\u1edbi Dox v\u00e0 Dox + Brev + Mdivi-1 so v\u1edbi Dox + Brev: ***P<\/em>\u00a0< 0,0005, **P<\/em>\u00a0< 0,005, *P<\/em>\u00a0< 0,05, trung b\u00ecnh \u00b1 SD.\u00a0N<\/em>\u00a0= 6\u20139.<\/p>\n<\/div>\n<\/div>\n<\/div>\n

Khi t\u00e1c d\u1ee5ng n\u00e0y c\u1ee7a breviscapine b\u1ecb Mdivi-1 ch\u1eb7n l\u1ea1i, n\u1ed3ng \u0111\u1ed9 ROS trong t\u1ebf b\u00e0o c\u01a1 tim \u0111\u00e3 t\u0103ng l\u00ean \u0111\u00e1ng k\u1ec3 (H\u00ecnh 6F<\/a>), trong khi s\u1ea3n xu\u1ea5t ATP gi\u1ea3m \u0111\u00e1ng k\u1ec3 (H\u00ecnh 6G<\/a>). H\u01a1n n\u1eefa, t\u1ef7 l\u1ec7 s\u1ed1ng s\u00f3t c\u1ee7a t\u1ebf b\u00e0o c\u01a1 tim \u0111\u00e3 gi\u1ea3m (H\u00ecnh b\u1ed5 sung S6<\/a>), v\u00e0 t\u00e1c d\u1ee5ng ph\u1ee5c h\u1ed3i c\u1ee7a breviscapine \u0111\u1ed1i v\u1edbi t\u1ebf b\u00e0o c\u01a1 tim b\u1ecb \u1ee9c ch\u1ebf. Khi Dox v\u00e0 Mdivi-1 \u0111\u01b0\u1ee3c k\u1ebft h\u1ee3p, vi\u1ec7c s\u1ea3n xu\u1ea5t ATP v\u00e0 t\u1ef7 l\u1ec7 s\u1ed1ng s\u00f3t c\u1ee7a c\u00e1c t\u1ebf b\u00e0o c\u01a1 tim c\u00e0ng gi\u1ea3m, n\u1ed3ng \u0111\u1ed9 ROS t\u0103ng l\u00ean v\u00e0 t\u1ed5n th\u01b0\u01a1ng c\u01a1 tim tr\u1edf n\u00ean tr\u1ea7m tr\u1ecdng h\u01a1n. Nh\u1eefng k\u1ebft qu\u1ea3 n\u00e0y cho th\u1ea5y r\u1eb1ng qu\u00e1 tr\u00ecnh t\u1ef1 th\u1ef1c c\u1ee7a ty th\u1ec3 \u0111\u00f3ng m\u1ed9t vai tr\u00f2 quan tr\u1ecdng trong t\u1ed5n th\u01b0\u01a1ng t\u1ebf b\u00e0o c\u01a1 tim do Dox g\u00e2y ra. Vi\u1ec7c t\u00e1i c\u1ea5u tr\u00fac m\u1ea1ng l\u01b0\u1edbi trao \u0111\u1ed5i ch\u1ea5t c\u1ee7a tim kh\u00f4ng th\u1ec3 b\u00f9 \u0111\u1eafp ho\u00e0n to\u00e0n t\u00ecnh tr\u1ea1ng r\u1ed1i lo\u1ea1n ch\u1ee9c n\u0103ng do t\u1ed5n th\u01b0\u01a1ng ty th\u1ec3 v\u00e0 t\u00e1c d\u1ee5ng b\u1ea3o v\u1ec7 c\u01a1 tim c\u1ee7a breviscapine ph\u1ee5 thu\u1ed9c v\u00e0o s\u1ef1 \u0111i\u1ec1u h\u00f2a chuy\u1ec3n h\u00f3a glucose v\u00e0 lipid c\u0169ng nh\u01b0 k\u00edch ho\u1ea1t qu\u00e1 tr\u00ecnh t\u1ef1 th\u1ef1c c\u1ee7a ty th\u1ec3. \u0110\u00e2y c\u0169ng c\u00f3 th\u1ec3 l\u00e0 l\u00fd do t\u1ea1i sao vi\u1ec7c \u0111i\u1ec1u ch\u1ec9nh m\u1ea1ng l\u01b0\u1edbi trao \u0111\u1ed5i ch\u1ea5t c\u1ee7a tim ch\u01b0a \u0111\u01b0\u1ee3c xem x\u00e9t li\u00ean quan \u0111\u1ebfn gi\u1ea3 thuy\u1ebft v\u1ec1 s\u1ef1 ph\u00e1t tri\u1ec3n DIC. C\u00f3 \u00fd ki\u1ebfn cho r\u1eb1ng vi\u1ec7c ng\u0103n ch\u1eb7n s\u1ef1 ti\u1ebfn tri\u1ec3n c\u1ee7a b\u1ec7nh v\u00e0 ph\u1ee5c h\u1ed3i ch\u1ee9c n\u0103ng tim c\u0169ng quan tr\u1ecdng nh\u01b0 nhau trong \u0111i\u1ec1u tr\u1ecb c\u00e1c tri\u1ec7u ch\u1ee9ng r\u1ed1i lo\u1ea1n ch\u1ee9c n\u0103ng tim v\u00e0 suy tim do Dox g\u00e2y ra, \u0111i\u1ec1u n\u00e0y c\u00f3 l\u1ee3i h\u01a1n cho ti\u00ean l\u01b0\u1ee3ng v\u00e0 ch\u1ea5t l\u01b0\u1ee3ng cu\u1ed9c s\u1ed1ng c\u1ee7a b\u1ec7nh nh\u00e2n.<\/p>\n<\/div>\n

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Breviscapine ph\u1ed1i h\u1ee3p v\u1edbi h\u00f3a tr\u1ecb li\u1ec7u ung th\u01b0 v\u00fa b\u1eb1ng c\u00e1ch gi\u1ea3m vi\u00eam v\u00e0 gi\u1ea3m th\u00e2m nhi\u1ec5m t\u1ebf b\u00e0o \u1ee9c ch\u1ebf mi\u1ec5n d\u1ecbch sau khi d\u00f9ng Dox<\/h3>\n

Theo l\u00fd thuy\u1ebft v\u1ec1 ngu\u1ed3n g\u1ed1c ty th\u1ec3, ty th\u1ec3 c\u00f3 ngu\u1ed3n g\u1ed1c t\u1eeb s\u1ef1 h\u1ee3p nh\u1ea5t c\u1ee7a vi khu\u1ea9n hi\u1ebfu kh\u00ed, ngh\u0129a l\u00e0 ty th\u1ec3 c\u00f3 \u0111\u1eb7c t\u00ednh l\u1ea1 (M\u00e0u x\u00e1m, 2012<\/a>). Khi ty th\u1ec3 b\u1ecb t\u1ed5n th\u01b0\u01a1ng, c\u00e1c m\u1eabu ph\u00e2n t\u1eed li\u00ean quan \u0111\u1ebfn t\u1ed5n th\u01b0\u01a1ng (DAMP) \u0111\u01b0\u1ee3c k\u00edch ho\u1ea1t, k\u00edch ho\u1ea1t ph\u1ea3n \u1ee9ng mi\u1ec5n d\u1ecbch c\u1ee7a c\u01a1 th\u1ec3 (Wilkins v\u00e0 c\u1ed9ng s\u1ef1, 2017<\/a>). Do \u0111\u00f3, ch\u00fang t\u00f4i \u0111\u01b0a ra gi\u1ea3 thuy\u1ebft r\u1eb1ng breviscapine th\u00fac \u0111\u1ea9y qu\u00e1 tr\u00ecnh thanh th\u1ea3i ty th\u1ec3 b\u1ecb t\u1ed5n th\u01b0\u01a1ng v\u00e0 gi\u00fap gi\u1ea3m vi\u00eam. K\u1ebft qu\u1ea3 cho th\u1ea5y n\u1ed3ng \u0111\u1ed9 trong huy\u1ebft thanh c\u1ee7a c\u00e1c cytokine g\u00e2y vi\u00eam interleukin-1\u03b2 (IL-1\u03b2), IL-6 v\u00e0 y\u1ebfu t\u1ed1 ho\u1ea1i t\u1eed kh\u1ed1i u \u03b1 (TNF-\u03b1) \u0111\u00e3 gi\u1ea3m \u0111\u00e1ng k\u1ec3 sau khi can thi\u1ec7p b\u1eb1ng breviscapine (H\u00ecnh 7A<\/a>) v\u00e0 nhu\u1ed9m mi\u1ec5n d\u1ecbch c\u00e1c m\u00f4 tim cho th\u1ea5y IL-1\u03b2 \u0111\u01b0\u1ee3c bi\u1ec3u hi\u1ec7n \u1edf m\u1ee9c \u0111\u1ed9 th\u1ea5p (H\u00ecnh b\u1ed5 sung S7<\/a>). Nh\u1eefng k\u1ebft qu\u1ea3 n\u00e0y cho th\u1ea5y breviscapine c\u00f3 th\u1ec3 l\u00e0m gi\u1ea3m s\u1ef1 b\u00e0i ti\u1ebft c\u00e1c y\u1ebfu t\u1ed1 g\u00e2y vi\u00eam v\u00e0 gi\u1ea3m ph\u1ea3n \u1ee9ng vi\u00eam \u1edf chu\u1ed9t ti\u1ebfp x\u00fac v\u1edbi Dox. C\u00e1c y\u1ebfu t\u1ed1 \u0111i\u1ec1u h\u00f2a vi\u00eam v\u00e0 t\u1ebf b\u00e0o t\u00e1c \u0111\u1ed9ng l\u00e0 nh\u1eefng th\u00e0nh ph\u1ea7n quan tr\u1ecdng c\u1ee7a vi m\u00f4i tr\u01b0\u1eddng kh\u1ed1i u v\u00e0 \u0111\u00f3ng vai tr\u00f2 quan tr\u1ecdng trong m\u1ed1i quan h\u1ec7 gi\u1eefa t\u00ecnh tr\u1ea1ng vi\u00eam v\u00e0 kh\u1ed1i u (Elinav v\u00e0 c\u1ed9ng s\u1ef1, 2013<\/a>;\u00a0Sautes-Fridman v\u00e0 c\u1ed9ng s\u1ef1, 2019<\/a>). T\u00ecnh tr\u1ea1ng vi\u00eam trong m\u00f4i tr\u01b0\u1eddng vi m\u00f4 kh\u1ed1i u c\u00f3 nhi\u1ec1u t\u00e1c \u0111\u1ed9ng kh\u00e1c nhau \u0111\u1ebfn kh\u1ed1i u, c\u00f3 th\u1ec3 th\u00fac \u0111\u1ea9y s\u1ef1 t\u0103ng sinh v\u00e0 s\u1ed1ng s\u00f3t c\u1ee7a c\u00e1c t\u1ebf b\u00e0o \u00e1c t\u00ednh, h\u00ecnh th\u00e0nh m\u1ea1ch v\u00e0 di c\u0103n; l\u00e0m suy y\u1ebfu ph\u1ea3n \u1ee9ng mi\u1ec5n d\u1ecbch m\u1eafc ph\u1ea3i c\u1ee7a c\u01a1 th\u1ec3; v\u00e0 thay \u0111\u1ed5i ph\u1ea3n \u1ee9ng c\u1ee7a c\u01a1 th\u1ec3 v\u1edbi hormone v\u00e0 thu\u1ed1c h\u00f3a tr\u1ecb (Iyengar v\u00e0 c\u1ed9ng s\u1ef1, 2016<\/a>;\u00a0Munn v\u00e0 Mellor, 2016<\/a>). Breviscapine l\u00e0m gi\u1ea3m vi\u00eam sau \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox nh\u01b0ng kh\u00f4ng \u1ea3nh h\u01b0\u1edfng \u0111\u1ebfn t\u00e1c d\u1ee5ng ti\u00eau di\u1ec7t t\u1ebf b\u00e0o ung th\u01b0 v\u00fa c\u1ee7a Dox\u00a0trong \u1ed1ng nghi\u1ec7m<\/em>\u00a0(H\u00ecnh 7B<\/a>). Li\u1ec7u n\u00f3 c\u00f3 th\u1ec3 gi\u00fap ng\u0103n ch\u1eb7n s\u1ef1 di chuy\u1ec3n c\u1ee7a c\u00e1c t\u1ebf b\u00e0o vi\u00eam \u0111\u1ebfn tr\u1ecdng t\u00e2m kh\u1ed1i u hay kh\u00f4ng, \u0111\u1eb7c bi\u1ec7t l\u00e0 trong vi\u1ec7c \u0111i\u1ec1u tr\u1ecb h\u1ee3p t\u00e1c c\u00e1c \u0111\u1ea1i th\u1ef1c b\u00e0o li\u00ean quan \u0111\u1ebfn kh\u1ed1i u (TAM), v\u1eabn ch\u01b0a r\u00f5 r\u00e0ng. TAM l\u00e0 c\u00e1c t\u1ebf b\u00e0o mi\u1ec5n d\u1ecbch x\u00e2m nh\u1eadp quan tr\u1ecdng v\u00e0 c\u00f3 th\u1ec3 chi\u1ebfm 50% t\u1ebf b\u00e0o kh\u1ed1i u trong ung th\u01b0 v\u00fa. TAM v\u00e0 c\u00e1c t\u1ebf b\u00e0o li\u00ean quan trong kh\u1ed1i u c\u1ee7a chu\u1ed9t v\u00e0 ng\u01b0\u1eddi th\u01b0\u1eddng l\u00e0 \u0111\u1ea1i th\u1ef1c b\u00e0o M2, ch\u00fang \u0111\u00e3 th\u00fac \u0111\u1ea9y s\u1ef1 ph\u00e1t tri\u1ec3n v\u00e0 h\u00ecnh th\u00e0nh m\u1ea1ch c\u1ee7a kh\u1ed1i u, t\u0103ng c\u01b0\u1eddng kh\u1ea3 n\u0103ng kh\u00e1ng tr\u1ecb v\u00e0 \u1ee9c ch\u1ebf kh\u1ea3 n\u0103ng mi\u1ec5n d\u1ecbch thu \u0111\u01b0\u1ee3c.Chen v\u00e0 c\u1ed9ng s\u1ef1, 2019<\/a>;\u00a0Pan v\u00e0 c\u1ed9ng s\u1ef1, 2020<\/a>). Gi\u1ea3m s\u1ef1 x\u00e2m nh\u1eadp c\u1ee7a TAM ho\u1eb7c \u0111\u1ed9 thanh th\u1ea3i TAM do thu\u1ed1c g\u00e2y ra l\u00e0 m\u1ed9t chi\u1ebfn l\u01b0\u1ee3c m\u1edbi n\u1ed5i trong li\u1ec7u ph\u00e1p mi\u1ec5n d\u1ecbch kh\u1ed1i u. V\u00ec v\u1eady, ch\u00fang t\u00f4i \u0111\u00e3 x\u00e2y d\u1ef1ng m\u00f4 h\u00ecnh chu\u1ed9t ung th\u01b0 v\u00fa 4T1 (H\u00ecnh 7C<\/a>). Chu\u1ed9t c\u00f3 kh\u1ed1i u 4T1\u00a0t\u1ea1i ch\u1ed7<\/em>\u00a0(200 mm3<\/sup>) \u0111\u01b0\u1ee3c chia ng\u1eabu nhi\u00ean th\u00e0nh 3 nh\u00f3m (N<\/em>\u00a0= 5) v\u00e0 ti\u00eam dung d\u1ecbch mu\u1ed1i \u0111\u1ec7m ph\u1ed1t ph\u00e1t (PBS), Dox ho\u1eb7c Dox + Brev. Dox v\u00e0 Brev \u0111\u01b0\u1ee3c d\u00f9ng v\u1edbi li\u1ec1u 10 mgkg\u22121<\/sup>\u00a0tr\u1ecdng l\u01b0\u1ee3ng c\u01a1 th\u1ec3 v\u00e0 1,4 mgkg\u22121<\/sup>\u00a0tr\u1ecdng l\u01b0\u1ee3ng c\u01a1 th\u1ec3, t\u01b0\u01a1ng \u1ee9ng. Nh\u1eefng con chu\u1ed9t b\u1ecb gi\u1ebft 7 ng\u00e0y sau khi \u0111i\u1ec1u tr\u1ecb v\u00e0 c\u00e1c kh\u1ed1i u \u0111\u01b0\u1ee3c thu th\u1eadp \u0111\u1ec3 \u0111\u00e1nh gi\u00e1 FCM v\u00e0 m\u00f4 h\u1ecdc. Sau khi \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox + Brev, t\u1ef7 l\u1ec7 \u0111\u1ea1i th\u1ef1c b\u00e0o li\u00ean quan \u0111\u1ebfn kh\u1ed1i u (TAM) x\u00e2m nh\u1eadp v\u00e0o kh\u1ed1i u \u0111\u00e3 gi\u1ea3m (H\u00ecnh 7D<\/a>). Nhu\u1ed9m m\u00f4 h\u1ecdc c\u1ee7a m\u00f4 kh\u1ed1i u cho th\u1ea5y bi\u1ec3u hi\u1ec7n th\u1ea5p h\u01a1n \u0111\u00e1ng k\u1ec3 c\u1ee7a d\u1ea5u hi\u1ec7u ki\u1ec3u h\u00ecnh M2 CD206 (H\u00ecnh 7E<\/a>). Kh\u1ed1i l\u01b0\u1ee3ng kh\u1ed1i u \u1edf chu\u1ed9t \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox + Brev th\u1ea5p h\u01a1n \u0111\u00e1ng k\u1ec3 so v\u1edbi chu\u1ed9t \u0111\u01b0\u1ee3c \u0111i\u1ec1u tr\u1ecb b\u1eb1ng Dox \u0111\u01a1n thu\u1ea7n (H\u00ecnh 7F<\/a>), cho th\u1ea5y r\u1eb1ng breviscapine c\u00f3 th\u1ec3 \u1ee9c ch\u1ebf s\u1ef1 ph\u00e1t tri\u1ec3n c\u1ee7a kh\u1ed1i u b\u1eb1ng c\u00e1ch gi\u1ea3m vi\u00eam v\u00e0 th\u00e2m nhi\u1ec5m TAM.<\/p>\n

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\"An<\/a><\/div>\n

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H\u00ccNH 7<\/a><\/div>\n
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(M\u1ed8T)<\/strong>\u00a0N\u1ed3ng \u0111\u1ed9 c\u00e1c cytokine g\u00e2y vi\u00eam IL-1\u03b2, IL-6 v\u00e0 TNF-\u03b1 trong huy\u1ebft thanh.\u00a0(B)<\/strong>\u00a0Kh\u1ea3 n\u0103ng s\u1ed1ng c\u1ee7a t\u1ebf b\u00e0o MCF-7\u00a0trong \u1ed1ng nghi\u1ec7m<\/em>.\u00a0(C)<\/strong>\u00a0S\u01a1 \u0111\u1ed3 \u0111i\u1ec1u tr\u1ecb chu\u1ed9t c\u00f3 kh\u1ed1i u.\u00a0(D)<\/strong>\u00a0C\u00e1c kh\u1ed1i u chu\u1ed9t \u0111\u00e3 \u0111\u01b0\u1ee3c thu th\u1eadp cho FCM.\u00a0(E)<\/strong>\u00a0Nhu\u1ed9m m\u00f4 h\u1ecdc c\u1ee7a c\u00e1c kh\u1ed1i u cho d\u1ea5u hi\u1ec7u ki\u1ec3u h\u00ecnh M2 CD206.\u00a0(F)<\/strong>\u00a0Trung b\u00ecnh c\u1ee7a t\u1ed5ng g\u00e1nh n\u1eb7ng kh\u1ed1i u. *P<\/em>\u00a0< 0,0005. Ki\u1ec3m so\u00e1t so v\u1edbi Dox, Dexra so v\u1edbi Dox v\u00e0 Brev so v\u1edbi Dox: ***P<\/em>\u00a0< 0,0005, **P<\/em>\u00a0< 0,005, *P<\/em>\u00a0< 0,05, trung b\u00ecnh \u00b1 SD.\u00a0N<\/em>\u00a0= 6\u20139.<\/p>\n

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\u0110i \u0111\u1ebfn:<\/a><\/div>\n

Cu\u1ed9c th\u1ea3o lu\u1eadn<\/h2>\n

Nghi\u00ean c\u1ee9u n\u00e0y cho th\u1ea5y r\u1ed1i lo\u1ea1n ch\u1ee9c n\u0103ng chuy\u1ec3n h\u00f3a glucose v\u00e0 lipid l\u00e0 \u0111\u1ed9ng l\u1ef1c quan tr\u1ecdng g\u00e2y nhi\u1ec5m \u0111\u1ed9c tim do anthracycline g\u00e2y ra v\u00e0 vi\u1ec7c ph\u1ee5c h\u1ed3i chuy\u1ec3n h\u00f3a \u1edf tim, th\u00fac \u0111\u1ea9y chuy\u1ec3n h\u00f3a glucose \u1edf c\u01a1 tim v\u00e0 c\u1ea3i thi\u1ec7n hi\u1ec7u qu\u1ea3 s\u1ea3n xu\u1ea5t n\u0103ng l\u01b0\u1ee3ng c\u1ee7a c\u01a1 tim l\u00e0 ph\u01b0\u01a1ng ph\u00e1p hi\u1ec7u qu\u1ea3 \u0111\u1ec3 ng\u0103n ng\u1eeba t\u00e1c d\u1ee5ng ph\u1ee5 tr\u00ean tim c\u1ee7a Dox. Ch\u00fang c\u00f3 th\u1ec3 th\u00fac \u0111\u1ea9y qu\u00e1 tr\u00ecnh t\u1ef1 th\u1ef1c b\u00e0o c\u1ee7a ty th\u1ec3, lo\u1ea1i b\u1ecf c\u00e1c ty th\u1ec3 b\u1ecb h\u01b0 h\u1ecfng. Gi\u1ea3m vi\u00eam gi\u00fap t\u0103ng c\u01b0\u1eddng t\u00e1c d\u1ee5ng ch\u1ed1ng ung th\u01b0 c\u1ee7a Dox.<\/p>\n

Tim c\u1ee7a \u0111\u1ed9ng v\u1eadt c\u00f3 v\u00fa s\u1eed d\u1ee5ng m\u1ed9t l\u01b0\u1ee3ng l\u1edbn n\u0103ng l\u01b0\u1ee3ng \u0111\u1ec3 co b\u00f3p li\u00ean t\u1ee5c v\u00e0 s\u1ef1 k\u1ebft h\u1ee3p ch\u1eb7t ch\u1ebd gi\u1eefa s\u1ea3n xu\u1ea5t ATP v\u00e0 co b\u00f3p c\u1ee7a tim l\u00e0 \u0111i\u1ec1u c\u1ea7n thi\u1ebft \u0111\u1ec3 tim ho\u1ea1t \u0111\u1ed9ng b\u00ecnh th\u01b0\u1eddng (Bertero v\u00e0 Maack, 2018<\/a>;\u00a0Timm v\u00e0 c\u1ed9ng s\u1ef1, 2018<\/a>). Qu\u00e1 tr\u00ecnh n\u00e0y \u0111\u00f2i h\u1ecfi s\u1ef1 \u0111i\u1ec1u ch\u1ec9nh ch\u00ednh x\u00e1c c\u1ee7a m\u1ea1ng l\u01b0\u1edbi chuy\u1ec3n h\u00f3a n\u0103ng l\u01b0\u1ee3ng c\u1ee7a tim. \u0110\u1eb7c \u0111i\u1ec3m n\u1ed5i b\u1eadt nh\u1ea5t c\u1ee7a m\u1ea1ng l\u01b0\u1edbi n\u00e0y l\u00e0 t\u00ednh linh ho\u1ea1t trao \u0111\u1ed5i ch\u1ea5t c\u1ee7a n\u00f3 \u0111\u1ec3 \u0111\u00e1p \u1ee9ng v\u1edbi nhi\u1ec1u k\u00edch th\u00edch kh\u00e1c nhau, bao g\u1ed3m nh\u1eefng thay \u0111\u1ed5i v\u1ec1 ph\u00e1t tri\u1ec3n v\u00e0 t\u00ecnh tr\u1ea1ng dinh d\u01b0\u1ee1ng, c\u0169ng nh\u01b0 kh\u1ea3 n\u0103ng c\u1ee7a tim trong vi\u1ec7c \u0111\u1ecbnh h\u00ecnh l\u1ea1i c\u00e1c con \u0111\u01b0\u1eddng trao \u0111\u1ed5i ch\u1ea5t \u0111\u1ec3 \u0111i\u1ec1u ch\u1ec9nh n\u0103ng l\u01b0\u1ee3ng v\u00e0 ch\u1ee9c n\u0103ng t\u00e2m thu c\u1ee7a c\u01a1 tim trong \u0111i\u1ec1u ki\u1ec7n sinh l\u00fd b\u1ec7nh m\u00e3n t\u00ednh.Bertero v\u00e0 Maack, 2018<\/a>;\u00a0Kim v\u00e0 c\u1ed9ng s\u1ef1, 2018<\/a>). S\u1ef1 t\u00e1i c\u1ea5u tr\u00fac trao \u0111\u1ed5i ch\u1ea5t n\u00e0y g\u00f3p ph\u1ea7n b\u1ea3o t\u1ed3n ch\u1ee9c n\u0103ng tim ho\u1eb7c \u0111\u1ea9y nhanh s\u1ef1 ti\u1ebfn tri\u1ec3n c\u1ee7a b\u1ec7nh. C\u00f3 nhi\u1ec1u nghi\u00ean c\u1ee9u v\u1ec1 c\u00e1c b\u1ec7nh l\u00fd tim m\u1ea1ch nh\u01b0 ph\u00ec \u0111\u1ea1i tim, suy tim nh\u01b0ng c\u00f3 r\u1ea5t \u00edt nghi\u00ean c\u1ee9u v\u1ec1 DIC. C\u00e1c nghi\u00ean c\u1ee9u tr\u01b0\u1edbc \u0111\u00e2y \u0111\u00e3 t\u1eadp trung v\u00e0o vi\u1ec7c s\u1ea3n xu\u1ea5t ROS v\u00e0 nh\u1eafm m\u1ee5c ti\u00eau topoisomerase II-\u03b2, d\u1eabn \u0111\u1ebfn t\u1ed5n th\u01b0\u01a1ng DNA, r\u1ed1i lo\u1ea1n ch\u1ee9c n\u0103ng ty th\u1ec3 v\u00e0 Ca2+<\/sup>\u00a0x\u1eed l\u00fd sai. Tuy nhi\u00ean, c\u00e1c ch\u1ea5t th\u1ea3i s\u1eaft l\u00e0m s\u1ea1ch ROS v\u00e0 dexra b\u1ed9 \u0111i\u1ec1u bi\u1ebfn topoisomerase II-\u03b2 kh\u00f4ng mang l\u1ea1i l\u1ee3i \u00edch \u0111\u00e1ng k\u1ec3, cho th\u1ea5y r\u1eb1ng c\u00e1c y\u1ebfu t\u1ed1 kh\u00e1c c\u0169ng c\u00f3 li\u00ean quan. Dox \u0111i\u1ec1u ch\u1ec9nh m\u1ea1ng l\u01b0\u1edbi trao \u0111\u1ed5i ch\u1ea5t trong c\u01a1 tim nh\u01b0 th\u1ebf n\u00e0o, vi\u1ec7c t\u00e1i c\u1ea5u tr\u00fac m\u1ea1ng l\u01b0\u1edbi trao \u0111\u1ed5i ch\u1ea5t n\u00e0y \u1ea3nh h\u01b0\u1edfng \u0111\u1ebfn hi\u1ec7u qu\u1ea3 s\u1ea3n xu\u1ea5t n\u0103ng l\u01b0\u1ee3ng c\u1ee7a tim nh\u01b0 th\u1ebf n\u00e0o v\u00e0 li\u1ec7u Dox c\u00f3 th\u00fac \u0111\u1ea9y \u0111\u1ed9c t\u00ednh tr\u00ean tim hay kh\u00f4ng v\u1eabn ch\u01b0a \u0111\u01b0\u1ee3c bi\u1ebft. C\u00e1c nghi\u00ean c\u1ee9u g\u1ea7n \u0111\u00e2y \u0111\u00e3 ti\u1ebft l\u1ed9 r\u1eb1ng b\u1ec7nh ferroptosis c\u1ee7a t\u1ebf b\u00e0o c\u01a1 tim do t\u00edch l\u0169y peroxid h\u00f3a lipid \u0111\u00f3ng m\u1ed9t vai tr\u00f2 quan tr\u1ecdng trong s\u1ef1 ti\u1ebfn tri\u1ec3n c\u1ee7a DIC, cho th\u1ea5y c\u00e1c t\u1ebf b\u00e0o c\u01a1 tim ti\u1ebfp x\u00fac v\u1edbi Dox c\u00f3 xu h\u01b0\u1edbng t\u0103ng c\u01b0\u1eddng chuy\u1ec3n h\u00f3a lipid (Xie v\u00e0 c\u1ed9ng s\u1ef1, 2021<\/a>;\u00a0Kitakata v\u00e0 c\u1ed9ng s\u1ef1, 2022<\/a>). Nh\u1eefng ph\u00e1t hi\u1ec7n c\u1ee7a ch\u00fang t\u00f4i l\u00e0m s\u00e1ng t\u1ecf th\u00eam r\u1eb1ng nhi\u1ec5m \u0111\u1ed9c tim do Dox g\u00e2y ra \u0111\u01b0\u1ee3c th\u00fac \u0111\u1ea9y b\u1edfi m\u1ed9t v\u00f2ng ph\u1ea3n h\u1ed3i lu\u1ea9n qu\u1ea9n v\u1ec1 r\u1ed1i lo\u1ea1n chuy\u1ec3n h\u00f3a glucose v\u00e0 lipid v\u00e0 d\u1eabn \u0111\u1ebfn t\u0103ng ti\u00eau th\u1ee5 oxy, s\u1ea3n xu\u1ea5t n\u0103ng l\u01b0\u1ee3ng k\u00e9m hi\u1ec7u qu\u1ea3 v\u00e0 t\u0103ng m\u1ee9c \u0111\u1ed9 c\u0103ng th\u1eb3ng oxy h\u00f3a.<\/p>\n

Breviscapine l\u00e0 lo\u1ea1i thu\u1ed1c c\u1ed5 \u0111i\u1ec3n \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng r\u1ed9ng r\u00e3i nh\u1ea5t \u0111\u1ec3 \u0111i\u1ec1u tr\u1ecb c\u00e1c b\u1ec7nh tim m\u1ea1ch v\u00e0 m\u1ea1ch m\u00e1u n\u00e3o \u1edf Trung Qu\u1ed1c, n\u00f3 \u0111\u01b0\u1ee3c \u0111\u01b0a v\u00e0o D\u01b0\u1ee3c \u0111i\u1ec3n Trung Qu\u1ed1c v\u00e0 Danh s\u00e1ch Thu\u1ed1c thi\u1ebft y\u1ebfu Qu\u1ed1c gia v\u00e0 l\u00e0 thu\u1ed1c thi\u1ebft y\u1ebfu \u0111\u1ec3 \u0111i\u1ec1u tr\u1ecb c\u1ea5p c\u1ee9u t\u1ea1i c\u00e1c b\u1ec7nh vi\u1ec7n Trung Qu\u1ed1c. Nghi\u00ean c\u1ee9u c\u1ee7a ch\u00fang t\u00f4i cho th\u1ea5y breviscapine c\u1ea3i thi\u1ec7n hi\u1ec7u qu\u1ea3 s\u1ea3n xu\u1ea5t ATP b\u1eb1ng c\u00e1ch \u0111i\u1ec1u ch\u1ec9nh m\u1ea1ch AKT serotonin-glycemia-c\u01a1 tim, \u0111\u1ecbnh h\u00ecnh l\u1ea1i qu\u00e1 tr\u00ecnh chuy\u1ec3n h\u00f3a n\u0103ng l\u01b0\u1ee3ng c\u1ee7a c\u01a1 tim, t\u0103ng s\u1eed d\u1ee5ng glucose v\u00e0 gi\u1ea3m qu\u00e1 tr\u00ecnh oxy h\u00f3a lipid. N\u00f3 l\u00e0m gi\u1ea3m t\u00e1c \u0111\u1ed9ng c\u1ee7a vi\u1ec7c s\u1ea3n xu\u1ea5t ATP th\u1ea5p, ti\u00eau th\u1ee5 oxy cao v\u00e0 c\u0103ng th\u1eb3ng oxy h\u00f3a cao do chuy\u1ec3n h\u00f3a kh\u00f4ng \u0111\u1ee7 l\u01b0\u1ee3ng l\u1edbn lipid trong tim do ti\u1ebfp x\u00fac v\u1edbi Dox, l\u00e0m gi\u1ea3m bi\u1ec3u hi\u1ec7n AMPK, ng\u0103n ch\u1eb7n v\u00f2ng lu\u1ea9n qu\u1ea9n c\u1ee7a vi\u1ec7c h\u1ea5p thu lipid qu\u00e1 m\u1ee9c trong c\u01a1 th\u1ec3. c\u01a1 tim v\u00e0 l\u00e0m ch\u1eadm s\u1ef1 ph\u00e1t tri\u1ec3n c\u1ee7a DIC (Kolwicz v\u00e0 Tian, 2011<\/a>). Ngo\u00e0i ra, k\u1ebft qu\u1ea3 c\u1ee7a ch\u00fang t\u00f4i cho th\u1ea5y serotonin c\u00f3 th\u1ec3 ho\u1ea1t \u0111\u1ed9ng nh\u01b0 m\u1ed9t nh\u00e1nh b\u1ed5 sung c\u1ee7a insulin \u0111\u1ec3 \u0111i\u1ec1u ch\u1ec9nh l\u01b0\u1ee3ng \u0111\u01b0\u1eddng trong m\u00e1u, cung c\u1ea5p l\u01b0\u1ee3ng \u0111\u01b0\u1eddng trong m\u00e1u cho tim v\u00e0 c\u00e1c c\u01a1 quan quan tr\u1ecdng kh\u00e1c trong \u0111i\u1ec1u ki\u1ec7n b\u1ec7nh l\u00fd. Serotonin c\u00f3 t\u00e1c d\u1ee5ng tr\u00e1i ng\u01b0\u1ee3c nhau trong vi\u1ec7c \u0111i\u1ec1u ch\u1ec9nh l\u01b0\u1ee3ng \u0111\u01b0\u1eddng trong m\u00e1u. M\u1ed9t m\u1eb7t, n\u00f3 t\u01b0\u01a1ng t\u00e1c v\u1edbi insulin \u0111\u1ec3 h\u1ea1 \u0111\u01b0\u1eddng huy\u1ebft; m\u1eb7t kh\u00e1c, n\u00f3 khi\u1ebfn c\u00e1c m\u00f4 kh\u00e1c ngo\u00e0i gan v\u00e0 c\u01a1 x\u01b0\u01a1ng h\u1ea5p th\u1ee5 glucose v\u00e0 l\u00e0m t\u0103ng l\u01b0\u1ee3ng \u0111\u01b0\u1eddng trong m\u00e1u. \u0110i\u1ec1u n\u00e0y cho th\u1ea5y r\u1eb1ng vi\u1ec7c gi\u1ea3m n\u1ed3ng \u0111\u1ed9 huy\u1ebft thanh ngo\u1ea1i vi, ch\u1eb3ng h\u1ea1n nh\u01b0 th\u00f4ng qua \u0111i\u1ec1u tr\u1ecb b\u1eb1ng breviscapine, c\u00f3 th\u1ec3 h\u1ed7 tr\u1ee3 vi\u1ec7c s\u1eed d\u1ee5ng glucose c\u1ee7a c\u00e1c c\u01a1 quan. Ngo\u00e0i ra, t\u00e1c d\u1ee5ng \u1ee9c ch\u1ebf c\u1ee7a breviscapine \u0111\u1ed1i v\u1edbi \u0111\u1ed9c t\u00ednh tr\u00ean tim ph\u1ee5 thu\u1ed9c v\u00e0o vi\u1ec7c t\u0103ng c\u01b0\u1eddng kh\u1ea3 n\u0103ng t\u1ef1 th\u1ef1c c\u1ee7a ty th\u1ec3, v\u00e0 vi\u1ec7c t\u00e1i c\u1ea5u tr\u00fac trao \u0111\u1ed5i ch\u1ea5t c\u1ee7a tim kh\u00f4ng th\u1ec3 d\u1eabn \u0111\u1ebfn gi\u1ea3i ph\u00f3ng ty th\u1ec3 t\u00edch l\u0169y trong b\u1ed1i c\u1ea3nh t\u1ed5n th\u01b0\u01a1ng tim do Dox g\u00e2y ra. Breviscapine g\u00e2y ra b\u1ec7nh t\u1ef1 k\u1ef7\u00a0trong c\u01a1 th\u1ec3 s\u1ed1ng<\/em>\u00a0\u0111\u1ec3 kh\u00f4i ph\u1ee5c c\u00e2n b\u1eb1ng n\u1ed9i m\u00f4i ty th\u1ec3 c\u1ee7a c\u01a1 tim th\u00f4ng qua con \u0111\u01b0\u1eddng PINK1\/Parkin, l\u00e0m gi\u1ea3m \u0111\u1ed9c t\u00ednh tr\u00ean tim do doxorubicin g\u00e2y ra. Xem x\u00e9t r\u1eb1ng vi\u1ec7c k\u00edch ho\u1ea1t autophagy c\u00f3 li\u00ean quan \u0111\u1ebfn s\u1ef1 xu\u1ea5t hi\u1ec7n v\u00e0 ph\u00e1t tri\u1ec3n c\u1ee7a nhi\u1ec1u lo\u1ea1i b\u1ec7nh, breviscapine c\u00f3 th\u1ec3 l\u00e0 m\u1ed9t lo\u1ea1i thu\u1ed1c \u1ee9ng c\u1eed vi\u00ean cho c\u00e1c b\u1ec7nh li\u00ean quan \u0111\u1ebfn autophagy c\u1ee7a ty th\u1ec3, mang l\u1ea1i gi\u00e1 tr\u1ecb \u1ee9ng d\u1ee5ng l\u00e2m s\u00e0ng r\u1ea5t t\u1ed1t. C\u00e1c nghi\u00ean c\u1ee9u g\u1ea7n \u0111\u00e2y \u0111\u00e3 ch\u1ec9 ra r\u1eb1ng breviscapine c\u00f3 t\u00e1c d\u1ee5ng \u1ee9c ch\u1ebf nh\u1ea5t \u0111\u1ecbnh \u0111\u1ed1i v\u1edbi s\u1ef1 ph\u00e1t tri\u1ec3n c\u1ee7a kh\u1ed1i u v\u00e0 ho\u1ea1t \u0111\u1ed9ng sinh h\u1ecdc c\u1ee7a t\u1ebf b\u00e0o kh\u1ed1i u (Ye v\u00e0 c\u1ed9ng s\u1ef1, 2020<\/a>). K\u1ebft qu\u1ea3 c\u1ee7a nghi\u00ean c\u1ee9u n\u00e0y cho th\u1ea5y breviscapine c\u00f3 th\u1ec3 ng\u0103n ng\u1eeba r\u1ed1i lo\u1ea1n ch\u1ee9c n\u0103ng tim do doxorubicin g\u00e2y ra trong m\u00f4 h\u00ecnh kh\u1ed1i u ung th\u01b0 v\u00fa v\u00e0 l\u00e0m gi\u1ea3m m\u1ee9c \u0111\u1ed9 c\u1ee7a c\u00e1c y\u1ebfu t\u1ed1 g\u00e2y vi\u00eam v\u00e0 th\u00e2m nhi\u1ec5m \u0111\u1ea1i th\u1ef1c b\u00e0o \u1ee9c ch\u1ebf mi\u1ec5n d\u1ecbch b\u1eb1ng c\u00e1ch lo\u1ea1i b\u1ecf ty th\u1ec3 b\u1ecb t\u1ed5n th\u01b0\u01a1ng, t\u1ea1o ra t\u00e1c d\u1ee5ng hi\u1ec7p \u0111\u1ed3ng v\u1edbi t\u00e1c d\u1ee5ng ch\u1ed1ng ung th\u01b0 c\u1ee7a doxorubicin. Breviscapine l\u00e0m gi\u1ea3m s\u1ef1 ph\u00e1t tri\u1ec3n c\u1ee7a kh\u1ed1i u b\u1eb1ng c\u00e1ch mang l\u1ea1i l\u1ee3i \u00edch \u0111i\u1ec1u tr\u1ecb k\u00e9p cho b\u1ec7nh ung th\u01b0, ng\u0103n ng\u1eeba \u0111\u1ed9c t\u00ednh tr\u00ean tim c\u1ee7a anthracycline. Breviscapine b\u1ea3o v\u1ec7 ch\u1ed1ng l\u1ea1i \u0111\u1ed9c t\u00ednh tr\u00ean tim do anthracycline g\u00e2y ra v\u00e0 c\u00f3 t\u00e1c d\u1ee5ng ch\u1ed1ng ung th\u01b0 hi\u1ec7p \u0111\u1ed3ng ch\u1ed1ng l\u1ea1i anthracycline, mang l\u1ea1i gi\u00e1 tr\u1ecb \u1ee9ng d\u1ee5ng l\u00e2m s\u00e0ng t\u1ed1t.<\/p>\n

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\u0110i \u0111\u1ebfn:<\/a><\/div>\n

S\u1ef1 nh\u00ecn nh\u1eadn<\/h2>\n
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C\u00e1c t\u00e1c gi\u1ea3 c\u1ea3m \u01a1n W-SS, Vi\u1ec7n Ung th\u01b0 thu\u1ed9c B\u1ec7nh vi\u1ec7n tr\u1ef1c thu\u1ed9c \u0110\u1ea1i h\u1ecdc Thanh \u0110\u1ea3o, Trung Qu\u1ed1c, v\u00ec \u0111\u00e3 chu\u1ea9n b\u1ecb d\u1ef1 th\u1ea3o ban \u0111\u1ea7u v\u00e0 qu\u1ea3n l\u00fd d\u1eef li\u1ec7u.<\/p>\n

 <\/p>\n<\/div>\n<\/div>\n

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\u0110i \u0111\u1ebfn:<\/a><\/div>\n

Tuy\u00ean b\u1ed1 v\u1ec1 t\u00ednh s\u1eb5n c\u00f3 c\u1ee7a d\u1eef li\u1ec7u<\/h2>\n

Nh\u1eefng \u0111\u00f3ng g\u00f3p ban \u0111\u1ea7u \u0111\u01b0\u1ee3c tr\u00ecnh b\u00e0y trong nghi\u00ean c\u1ee9u \u0111\u01b0\u1ee3c bao g\u1ed3m trong b\u00e0i b\u00e1o\/T\u00e0i li\u1ec7u b\u1ed5 sung<\/a>; y\u00eau c\u1ea7u th\u00eam c\u00f3 th\u1ec3 \u0111\u01b0\u1ee3c chuy\u1ec3n \u0111\u1ebfn t\u00e1c gi\u1ea3 t\u01b0\u01a1ng \u1ee9ng.<\/p>\n

 <\/p>\n<\/div>\n

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\u0110i \u0111\u1ebfn:<\/a><\/div>\n

Chu\u1ea9n m\u1ef1c \u0111\u1ea1o \u0111\u1ee9c<\/h2>\n

C\u00e1c nghi\u00ean c\u1ee9u li\u00ean quan \u0111\u1ebfn ng\u01b0\u1eddi tham gia \u0111\u00e3 \u0111\u01b0\u1ee3c \u1ee6y ban \u0110\u1ea1o \u0111\u1ee9c c\u1ee7a B\u1ec7nh vi\u1ec7n tr\u1ef1c thu\u1ed9c \u0110\u1ea1i h\u1ecdc Thanh \u0110\u1ea3o xem x\u00e9t v\u00e0 ph\u00ea duy\u1ec7t. C\u00e1c b\u1ec7nh nh\u00e2n\/ng\u01b0\u1eddi tham gia \u0111\u00e3 cung c\u1ea5p s\u1ef1 \u0111\u1ed3ng \u00fd b\u1eb1ng v\u0103n b\u1ea3n \u0111\u1ec3 tham gia v\u00e0o nghi\u00ean c\u1ee9u n\u00e0y. Nghi\u00ean c\u1ee9u tr\u00ean \u0111\u1ed9ng v\u1eadt \u0111\u00e3 \u0111\u01b0\u1ee3c xem x\u00e9t v\u00e0 ph\u00ea duy\u1ec7t b\u1edfi \u1ee6y ban \u0110\u1ea1o \u0111\u1ee9c c\u1ee7a Tr\u01b0\u1eddng Cao \u0111\u1eb3ng Y t\u1ebf thu\u1ed9c \u0110\u1ea1i h\u1ecdc Thanh \u0110\u1ea3o.<\/p>\n

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\u0110i \u0111\u1ebfn:<\/a><\/div>\n

S\u1ef1 \u0111\u00f3ng g\u00f3p c\u1ee7a t\u00e1c gi\u1ea3<\/h2>\n

M-JL v\u00e0 W-SS \u0111\u00e3 v\u1eadn h\u00e0nh t\u1ea5t c\u1ea3 c\u00e1c th\u1eed nghi\u1ec7m, ph\u00e2n t\u00edch d\u1eef li\u1ec7u v\u00e0 vi\u1ebft b\u1ea3n th\u1ea3o g\u1ed1c. Y-KZ \u0111\u00e3 ph\u00e2n t\u00edch d\u1eef li\u1ec7u v\u00e0 vi\u1ebft b\u1ea3n th\u1ea3o g\u1ed1c. YY \u0111\u00e3 ph\u00e2n t\u00edch d\u1eef li\u1ec7u. QL ph\u00e2n t\u00edch v\u00e0 gi\u1ea3i th\u00edch d\u1eef li\u1ec7u c\u1ee7a \u0111\u1ed9ng v\u1eadt. Y-ZG v\u1eadn h\u00e0nh c\u00e1c th\u00ed nghi\u1ec7m tr\u00ean \u0111\u1ed9ng v\u1eadt. TY v\u1eadn h\u00e0nh c\u00e1c th\u00ed nghi\u1ec7m tr\u00ean \u0111\u1ed9ng v\u1eadt. D-MX -xem x\u00e9t v\u00e0 ch\u1ec9nh s\u1eeda b\u1ea3n th\u1ea3o. T\u1ea5t c\u1ea3 c\u00e1c t\u00e1c gi\u1ea3 \u0111\u1ec1u \u0111\u1ecdc v\u00e0 ph\u00ea duy\u1ec7t b\u1ea3n th\u1ea3o cu\u1ed1i c\u00f9ng.<\/p>\n

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\u0110i \u0111\u1ebfn:<\/a><\/div>\n

Kinh ph\u00ed<\/h2>\n

Nghi\u00ean c\u1ee9u n\u00e0y \u0111\u00e3 nh\u1eadn \u0111\u01b0\u1ee3c m\u1ed9t kho\u1ea3n t\u00e0i tr\u1ee3 c\u1ee5 th\u1ec3 t\u1eeb c\u00e1c c\u01a1 quan t\u00e0i tr\u1ee3 trong t\u1ed5 ch\u1ee9c ung th\u01b0 Thanh \u0110\u1ea3o v\u00e0 D\u1ef1 \u00e1n nghi\u00ean c\u1ee9u \u1ee9ng d\u1ee5ng sau ti\u1ebfn s\u0129 Thanh \u0110\u1ea3o (s\u1ed1 RZ2100005362).<\/p>\n

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\u0110i \u0111\u1ebfn:<\/a><\/div>\n

Xung \u0111\u1ed9t l\u1ee3i \u00edch<\/h2>\n

C\u00e1c t\u00e1c gi\u1ea3 tuy\u00ean b\u1ed1 r\u1eb1ng nghi\u00ean c\u1ee9u \u0111\u01b0\u1ee3c th\u1ef1c hi\u1ec7n trong tr\u01b0\u1eddng h\u1ee3p kh\u00f4ng c\u00f3 b\u1ea5t k\u1ef3 m\u1ed1i quan h\u1ec7 th\u01b0\u01a1ng m\u1ea1i ho\u1eb7c t\u00e0i ch\u00ednh n\u00e0o c\u00f3 th\u1ec3 \u0111\u01b0\u1ee3c hi\u1ec3u l\u00e0 xung \u0111\u1ed9t l\u1ee3i \u00edch ti\u1ec1m \u1ea9n.<\/p>\n

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\u0110i \u0111\u1ebfn:<\/a><\/div>\n

Ghi ch\u00fa c\u1ee7a nh\u00e0 xu\u1ea5t b\u1ea3n<\/h2>\n

T\u1ea5t c\u1ea3 c\u00e1c tuy\u00ean b\u1ed1 \u0111\u01b0\u1ee3c tr\u00ecnh b\u00e0y trong b\u00e0i vi\u1ebft n\u00e0y ch\u1ec9 l\u00e0 c\u1ee7a c\u00e1c t\u00e1c gi\u1ea3 v\u00e0 kh\u00f4ng nh\u1ea5t thi\u1ebft \u0111\u1ea1i di\u1ec7n cho tuy\u00ean b\u1ed1 c\u1ee7a c\u00e1c t\u1ed5 ch\u1ee9c li\u00ean k\u1ebft c\u1ee7a h\u1ecd ho\u1eb7c c\u1ee7a nh\u00e0 xu\u1ea5t b\u1ea3n, ng\u01b0\u1eddi bi\u00ean t\u1eadp v\u00e0 ng\u01b0\u1eddi \u0111\u00e1nh gi\u00e1. B\u1ea5t k\u1ef3 s\u1ea3n ph\u1ea9m n\u00e0o c\u00f3 th\u1ec3 \u0111\u01b0\u1ee3c \u0111\u00e1nh gi\u00e1 trong b\u00e0i vi\u1ebft n\u00e0y ho\u1eb7c tuy\u00ean b\u1ed1 c\u00f3 th\u1ec3 do nh\u00e0 s\u1ea3n xu\u1ea5t \u0111\u01b0a ra \u0111\u1ec1u kh\u00f4ng \u0111\u01b0\u1ee3c nh\u00e0 xu\u1ea5t b\u1ea3n b\u1ea3o \u0111\u1ea3m ho\u1eb7c x\u00e1c nh\u1eadn.<\/p>\n

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\u0110i \u0111\u1ebfn:<\/a><\/div>\n

T\u00e0i li\u1ec7u b\u1ed5 sung<\/h2>\n

T\u00e0i li\u1ec7u b\u1ed5 sung cho b\u00e0i vi\u1ebft n\u00e0y c\u00f3 th\u1ec3 \u0111\u01b0\u1ee3c t\u00ecm th\u1ea5y tr\u1ef1c tuy\u1ebfn t\u1ea1i:\u00a0https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.930835\/full#supplementary-material<\/a><\/p>\n

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Nh\u1ea5n v\u00e0o \u0111\u00e2y \u0111\u1ec3 th\u00eam t\u1eadp tin d\u1eef li\u1ec7u.<\/a>(2,5 tri\u1ec7u, DOCX)<\/sup><\/div>\n
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\u0110i \u0111\u1ebfn:<\/a><\/div>\n

Ng\u01b0\u1eddi gi\u1edbi thi\u1ec7u<\/h2>\n

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