钠-葡萄糖协同转运蛋白2抑制剂对足细胞自噬影响及其肾脏保护机制的研究进展

Research progress on the effectof SGLT2 inhibitor to podocyte autophagy and its renal protective mechanism

DKD在我国逐渐成为终末期肾病的主要病因,高血糖对足细胞的损伤是DKD/蛋白尿/肾损伤的关键环节,自噬在维持足细胞稳态方面起关键作用,而自噬与能量代谢密切相关。SGLT2i是全新机制的降糖药物,对于肾脏的保护大于降低血糖的作用。有文献阐述应用SGLT2i可能模拟营养剥夺状态,从而通过活化单磷酸腺苷激活的蛋白激酶、沉默信息调节因子2相关酶1通路增强肾脏自噬通量,与肾脏足细胞自噬也存在相关性。本文对SGLT2i对足细胞自噬影响及其肾脏保护机制的研究进展进行综述,旨在阐明SGLT2i肾脏保护机制。

Diabetic kidney disease(DKD)has gradually become the main cause of end-stage renal disease(ESRD)in China. The damage of podocytes caused by high blood glucose is a key step in DKD/proteinuria/kidney injury. Autophagy plays a key role in maintaining podocyte homeostasis,and closely related to energy metabolism. Sodium-glucose cotransporter-2 inhibitors(SGLT2i)are hypoglycemic drugs with new mechanism. Its protective effect on kidney exceeds its effect on blood glucose control. There are literatures illustrating that the application of SGLT2i may mimic the state of nutrient deprivation,thereby activate the AMPK and SIRT1 pathways and enhance renal autophagy flux. SGLT2i may have a close relationship with renal podocyte autophagy. Here,we reviewed the effects of SGLT2i on podocyte autophagy,aiming at clarifying the renal protective mechanism of SGLT2i.