Ginsenoside Rb1 attenuates cardiomyocyte apoptosis induced by myocardial ischemia reperfusion injury through mTOR signal pathway
Ginsenoside Rb1 attenuates cardiomyocyte apoptosis induced by myocardial ischemia reperfusion injury through mTOR signal pathway
复制标题
人参皂苷Rb1通过mTOR信号通路减轻心肌缺血再灌注损伤诱导的心肌细胞凋亡
DOI：
10.1016/j.biopha.2020.109913
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发表时间：
2020-05-01
影响因子：
7.5
通讯作者：
Lu, Di
中科院分区：
文献类型：
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作者：
Li, Chang-Yan;Yang, Ping;Lu, Di
目的：人参皂苷Rb 1（Ginsenoside Rb 1，GRb 1）对心肌梗死具有明显的保护作用，但其治疗心肌缺血再灌注损伤的机制尚不清楚。本研究旨在探讨GRb_1预处理对大鼠心肌I/R损伤的保护机制。方法和结果：GRb_1预处理可改善心肌I/R损伤所致的心功能，包括LVDP、-dp/dt min和+ dp/dt max，但心率（HR）维持在与I/R组相当的水平。另外，I/R损伤组给予GRb 1预处理后，心肌酶（CK MB、Trop 1）和CtsB的释放减少。此外，GRb 1还可降低细胞凋亡相关蛋白如切割型caspase 3的表达，降低与抗凋亡相关的Bcl-2/Bax比值。通过在GRb 1预处理之前腹腔内注射雷帕霉素来扩展该研究。因此，与I/R相比，GRb 1预处理后mTOR通路显著上调。值得注意的是，雷帕霉素减弱了GRb 1预处理的抗凋亡保护作用。结论：GRb 1预处理可减轻心肌I/R损伤，表现为心功能指标的改善，同时减少心肌酶CK MB、Trop 1和CtsB的释放。更重要的是，我们已经表明，GRb 1对I/R损伤诱导的心肌细胞凋亡的保护作用与mTOR信号通路的激活有关，如通过使用雷帕霉素所证明的。
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.