二甲双胍在糖尿病性肾病中的肾脏保护机制

Nephroprotectant Mechanisms of Metformin in Diabetes Nephropathy

二甲双胍以良好的降血糖效果和不良反应少而闻名。二甲双胍主要通过AMP活化的蛋白激酶(AMPK)通路的激活来发挥作用。高血糖和蛋白尿条件下,AMPK和自噬等肾脏细胞防御机制失活,肾脏细胞病理机制相继激活,如哺乳动物雷帕霉素靶蛋白通路,内质网应激,上皮-间充质转化,氧化应激和缺氧等。除了降低血糖以外,二甲双胍可在一定程度上起到保护肾脏作用。现就二甲双胍保护肾脏的多种作用机制,以及二甲双胍用于糖尿病肾病和其他非糖尿病性慢性肾病肾保护作用的研究进行综述。

Metformin,a well-known anti-diabetic agent,is very effective in lowering blood glucose in patients with type2 diabetes with minimal side effects. Metformin elicits its therapeutic effects mainly via activation of AMP-activated protein kinase（ AMPK） pathway. Under the conditions of hyperglycemia and proteinuria,renal cell defense mechanisms such as AMPK and autophagy are inactivated,and the pathological mechanisms of renal cells are activated in succession,such as mammalian rapamycin target protein pathway,endoplasmic reticulum stress,epithelial cell mesenchymal transformation,oxidative stress and hypoxia. In addition to lowering blood sugar,numerous studies have shown that metformin plays a protective role in kidney to some extent. Here is to make a review of the various mechanisms by which metformin protects renal cells and the role of metformin for patients with diabetic nephropathy and other non-diabetic chronic kidney disease.