Metformin (Met) is a major widely used oral glucose lowering drug for the treatment of type 2 diabetes. It is reported that metformin could regulate autophagy in various diseases of cardiovascular system including in I/R injury, diabetic cardiomyopathy and heart failure. Autophagy plays a controversial role in ischemia/reperfusion (I/R) injury, and this research was performed to explore the cardioprotective effect of Met on I/R injury and discuss the underlying mechanism of autophagy in it. In vivo and in vitro, Met exerted cardioprotection function of decreasing myocardial inflammation and apoptosis with a decrease in the level of autophagy. Moreover, Met significantly inhibited autophagosome formation and restore the impairment of autophagosome processing, which lead to cardioprotection effect of Met. Akt was up-regulated in Met-treated I/R hearts and miransertib, a pan-AKT inhibitor, was able to reverse the alleviating autophagy effect of Met. We demonstrate that Met protects cardiomyocytes from I/R-induced apoptosis and inflammation through down regulation of autophagy mediated by Akt signaling pathway.

中文翻译：

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二甲双胍通过在缺血-再灌注损伤模型中抑制自噬来抑制心肌细胞的炎症和凋亡。

二甲双胍（Met）是一种广泛使用的主要口服降糖药物，用于治疗 2 型糖尿病。据报道，二甲双胍可以调节心血管系统各种疾病的自噬，包括 I/R 损伤、糖尿病心肌病和心力衰竭。自噬在缺血/再灌注 (I/R) 损伤中扮演着有争议的角色，本研究旨在探讨 Met 对 I/R 损伤的心脏保护作用，并讨论自噬在其中的潜在机制。体内和体外, Met通过降低自噬水平发挥减少心肌炎症和细胞凋亡的心脏保护功能。此外，Met 显着抑制自噬体的形成并恢复自噬体加工的损伤，从而导致 Met 的心脏保护作用。Akt 在 Met 治疗的 I/R 心脏中上调，而 miransertib（一种泛 AKT 抑制剂）能够逆转 Met 的自噬缓解作用。我们证明 Met 通过下调 Akt 信号通路介导的自噬来保护心肌细胞免受 I/R 诱导的细胞凋亡和炎症的影响。