Ginsenoside Rb1 attenuates cardiomyocyte apoptosis induced by myocardial ischemia reperfusion injury through mTOR signal pathway

BIOMEDICINE & PHARMACOTHERAPY(2020)

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摘要
Objective: Ginsenoside Rb1 (GRb1) is known to play an effective protection on myocardial infarction, yet its therapeutic mechanism on myocardial ischemia/reperfusion (I/R) injury has remained obscure. Here we sought to investigate the protective mechanism of GRb1 preconditioning on myocardial I/R injury in rats. Methods and results: We report here that GRb1 preconditioning could improve myocardial I/R injury induced-cardiac functions including LVDP, -dp/dt min and + dp/dt max; however, the heart rate (HR) was maintained at a level comparable to the I/R group. Additionally, in I/R injury group given GRb1 preconditioning, release of myocardial enzymes (CK-MB and Trop 1) and CtsB was decreased. Moreover, GRb1 decreased the expression of apoptotic related proteins e.g. cleaved-caspase 3; however, the ratio of Bcl-2/Bax related to anti-apoptosis was decreased. The study was extended by injecting rapamycin intraperitoneally before GRb1 pretreatment. Thus, mTOR pathway was significantly upregulated after GRb1 pretreatment when compared with I/R. Remarkably, the anti-apoptosis protection of GRb1 pretreatment was attenuated by rapamycin. Furthermore, GRb1 effectively reduced the infarct size thus supporting its role in anti-myocardial I/R injury. Conclusions: It is concluded that GRb1 preconditioning can ameliorate myocardial I/R injury as manifested by the improvement of cardiac function indices; moreover, release of myocardial enzymes, namely, CK-MB, Trop 1 and CtsB was reduced. More importantly, we have shown that the protective effect of GRb1 against I/R injury induced cardiomyocyte apoptosis is associated with the activation of mTOR signal pathway as evident by the use of rapamycin.
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关键词
Apoptosis,mTOR,Myocardial ischemia reperfusion injury,Ginsenoside Rb1
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