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人参皂苷Rg3通过激活AMPK介导的自噬保护心脏免受异丙肾上腺素诱导的心肌梗死。

Ginsenoside Rg3 protects heart against isoproterenol-induced myocardial infarction by activating AMPK mediated autophagy.

作者信息

Sun Gui-Zhi, Meng Fan-Ji, Cai Huai-Qiu, Diao Xue-Bo, Zhang Bo, Bai Xiu-Ping

机构信息

Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.

Department of Ultrasonography, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.

出版信息

Cardiovasc Diagn Ther. 2020 Apr;10(2):153-160. doi: 10.21037/cdt.2020.01.02.

Abstract

BACKGROUND

Panax ginseng is a well-known medicinal herb that is widely used in traditional Chinese medicine for treating various diseases. Ginsenoside Rg3 (Rg3) is thought to be one of the most important active ingredients of Panax ginseng. However, the molecular mechanism underlying the beneficial effects of Rg3 has been elusive.

METHODS

In the mouse heart injury model induced by isoproterenol (ISO), we used brain natriuretic peptide (BNP), lactate dehydrogenase (LDH) and caspase-3 ELISA kits to test myocardium injury. To test whether Rg3 protects myocardial injury through AMPK mediated autophagy, we used specific AMPK inhibitor in combination with Rg3. NLRP3 inflammasome related molecules such as NLRP3, ASC and caspase-1 were measured by western-blot following Rg3 treatment.

RESULTS

We found that Rg3 significantly reduced ISO induced myocardial injury indicated by the downregulation of serum BNP and LDH. In addition, we showed that the improvement of myocardial injury by Rg3 was associated with enhanced expression of autophagy related protein and activation of AMPK downstream signaling pathway.

CONCLUSIONS

We observed that inhibition of AMPK significantly reversed the myocardial protective effect of Rg3, which is associated with a decrease of Rg3 induced autophagy. These together suggested that Rg3 may improve myocardial injury during MI through AMPK mediated autophagy. Our study also provides important translational evidence for using Rg3 in treating myocardial infarction (MI).

摘要

背景

人参是一种著名的草药,在传统中医中广泛用于治疗各种疾病。人参皂苷Rg3(Rg3)被认为是人参最重要的活性成分之一。然而,Rg3有益作用的分子机制一直难以捉摸。

方法

在异丙肾上腺素(ISO)诱导的小鼠心脏损伤模型中,我们使用脑钠肽(BNP)、乳酸脱氢酶(LDH)和半胱天冬酶-3 ELISA试剂盒检测心肌损伤。为了测试Rg3是否通过AMPK介导的自噬保护心肌损伤,我们将特异性AMPK抑制剂与Rg3联合使用。Rg3处理后,通过蛋白质免疫印迹法检测NLRP3炎性小体相关分子,如NLRP3、ASC和半胱天冬酶-1。

结果

我们发现Rg3显著减轻了ISO诱导的心肌损伤,表现为血清BNP和LDH水平下调。此外,我们表明Rg3对心肌损伤的改善与自噬相关蛋白表达增强和AMPK下游信号通路激活有关。

结论

我们观察到抑制AMPK可显著逆转Rg3的心肌保护作用,这与Rg3诱导的自噬减少有关。这些结果共同表明,Rg3可能通过AMPK介导的自噬改善心肌梗死(MI)期间的心肌损伤。我们的研究还为使用Rg3治疗心肌梗死提供了重要的转化证据。

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