二甲双胍基于AMPK保护缺血再灌注心肌损伤的研究进展

Research Progress on Metformin Protection against Ischemic Reperfusion Myocardial In-jury Based on AMPK Pathway

心肌缺血再灌注损伤(MIRI)是指缺血的心肌在恢复血液再灌注后,反而使心肌出现代谢紊乱和结构损伤,引起细胞死亡,造成心脏功能进一步损害的现象。心肌缺血缺氧导致细胞内AMP升高,AMP依赖的蛋白激酶(AMP-activated protein kinase, AMPK)信号通路被激活。越来越多的文献表明,AMPK的激活对心脏的缺血再灌注(I/R)损伤具有保护作用。二甲双胍是治疗2型糖尿病最常用且首选的口服降糖药,疗效安全稳定。已有研究证明二甲双胍可以通过激活AMPK的方式来调节多种信号传导通路,通过调节能力代谢、抗氧化应激、减轻炎症反应、调节自噬、抑制细胞凋亡以减轻I/R损伤,为临床实践提供了参考依据。二甲双胍展现出成为治疗MIRI理想药物的潜力,但当前仍需进行更多的临床试验以深入研究其有效性。

Myocardial ischemia-reperfusion injury (MIRI) refers to the phenomenon where the myocardium, after being reperfused following a period of ischemia, experiences metabolic disorders and struc-tural damage leading to cell death and further impairment of cardiac function. Ischemic conditions in the myocardium lead to an increase in intracellular AMP, which activates the AMP-activated pro-tein kinase (AMPK) signaling pathway. Increasing evidence suggests that the activation of AMPK plays a protective role against ischemia-reperfusion (I/R) injury in the heart. Metformin, the most commonly used and preferred oral hypoglycemic agent for treating type 2 diabetes, has shown to be safe and effective. Studies have demonstrated that metformin can regulate multiple signaling pathways by activating AMPK, modulating energy metabolism, counteracting oxidative stress, re-ducing inflammatory responses, regulating autophagy, and inhibiting apoptosis to alleviate I/R in-jury. This provides a reference for clinical practice. Metformin shows potential as an ideal drug for treating MIRI, but further clinical trials are needed to explore its effectiveness in-depth.