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二甲双胍的心脏保护作用。

The cardioprotective effects of metformin.

机构信息

Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.

出版信息

Curr Opin Lipidol. 2011 Dec;22(6):445-53. doi: 10.1097/MOL.0b013e32834ae1a7.

Abstract

PURPOSE OF REVIEW

In patients with type 2 diabetes mellitus, treatment with metformin is associated with a lower cardiovascular morbidity and mortality, compared with alternative glucose-lowering drugs. It has been suggested that metformin might exert direct protective effects on the heart.

RECENT FINDINGS

This review appraises recent experimental animal studies on the effect of metformin on myocardial ischaemia-reperfusion injury and remodeling. In murine models of myocardial infarction, the administration of metformin potently limits infarct size. Activation of adenosine monophosphate-activated protein kinase, increased formation of adenosine, and the prevention of opening of the mitochondrial permeability transition pore at reperfusion all contribute to this cardioprotective effect. In addition, metformin therapy attenuates postinfarction cardiac remodeling. There is evidence that activation of adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase, and a reduced collagen expression are crucial for this effect.

SUMMARY

The finding that metformin limits myocardial infarct size and remodeling in animal models of myocardial infarction suggests that patients suffering from myocardial ischaemia could benefit from treatment with metformin, even when these patients do not have diabetes. Currently, several clinical trials are being performed to test this hypothesis.

摘要

目的综述

与其他降血糖药物相比,在 2 型糖尿病患者中,使用二甲双胍治疗与较低的心血管发病率和死亡率相关。有人提出,二甲双胍可能对心脏有直接的保护作用。

最近发现

本综述评价了最近关于二甲双胍对心肌缺血再灌注损伤和重构影响的实验动物研究。在心肌梗死的鼠模型中,给予二甲双胍可显著限制梗死面积。在再灌注时,AMP 激活的蛋白激酶的激活、腺苷的形成增加以及线粒体通透性转换孔的开放的预防,都有助于这种心脏保护作用。此外,二甲双胍治疗可减轻梗死后的心脏重构。有证据表明,AMP 激活的蛋白激酶和内皮型一氧化氮合酶的激活以及胶原蛋白表达的减少对这种作用至关重要。

总结

在心肌梗死的动物模型中,二甲双胍限制心肌梗死面积和重构的发现表明,即使这些患者没有糖尿病,患有心肌缺血的患者也可能从二甲双胍治疗中获益。目前,正在进行几项临床试验来检验这一假设。

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