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人参皂苷 Rb1 通过 mTOR 信号通路减轻心肌缺血再灌注损伤引起的心肌细胞凋亡。

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

机构信息

Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, China.

Department of Cardiology, the Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China.

出版信息

Biomed Pharmacother. 2020 May;125:109913. doi: 10.1016/j.biopha.2020.109913. Epub 2020 Jan 29.

DOI:10.1016/j.biopha.2020.109913
PMID:32006902
Abstract

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 l) 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 l 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.

摘要

目的

人参皂苷 Rb1(GRb1)已知对心肌梗死有有效保护作用,但它对心肌缺血/再灌注(I/R)损伤的治疗机制仍不清楚。在这里,我们试图研究 GRb1 预处理对大鼠心肌 I/R 损伤的保护机制。

方法和结果

我们在这里报告,GRb1 预处理可以改善心肌 I/R 损伤引起的心脏功能,包括 LVDP、-dp/dt min 和+dp/dt max;然而,心率(HR)保持在与 I/R 组相当的水平。此外,在给予 GRb1 预处理的 I/R 损伤组中,心肌酶(CK-MB 和 Trop l)和 CtsB 的释放减少。此外,GRb1 降低了凋亡相关蛋白的表达,例如裂解的 caspase 3;然而,与抗凋亡相关的 Bcl-2/Bax 比值降低。该研究通过在 GRb1 预处理前腹腔内注射雷帕霉素进一步扩展。因此,与 I/R 相比,GRb1 预处理后 mTOR 通路显著上调。值得注意的是,雷帕霉素减弱了 GRb1 预处理的抗凋亡保护作用。此外,GRb1 有效减少了梗死面积,从而支持其在抗心肌 I/R 损伤中的作用。

结论

GRb1 预处理可以改善心肌 I/R 损伤,表现为心脏功能指标的改善;此外,心肌酶,即 CK-MB、Trop l 和 CtsB 的释放减少。更重要的是,我们已经表明,GRb1 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,这可以通过使用雷帕霉素来证明。

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