达格列净促进糖尿病肾脏病足细胞自噬的机制

Mechanism of dagliflozin in promoting podocyte autophagy in diabetic kidney disease

蛋白尿是糖尿病肾脏病的特征性表现和重要的疾病进展风险因素,会引起肾功能恶化直至肾衰竭,与终末期肾脏病和心血管疾病的风险增加相关。足细胞是肾小球滤过屏障的重要组成部分之一,足细胞损伤是蛋白尿发生的主要原因。自噬作为维持足细胞稳态的重要机制,与体内营养状态密切相关。达格列净是钠-葡萄糖协同转运体2抑制剂,具有肾脏保护作用,有研究表明该药可通过模拟营养剥夺状态、抑制哺乳动物雷帕霉素靶蛋白1,并激活腺苷酸活化蛋白激酶、沉默信息调节因子1,从而增强足细胞自噬和减少蛋白尿。本文就达格列净通过营养感应信号通路促进糖尿病肾脏病足细胞自噬从而起到保护肾功能的作用进行系统性综述,为糖尿病肾脏病的预防和治疗提供可行的临床应用和未来的研究建议。

Proteinuria is a characteristic manifestation of diabetic kidney disease and an important risk factor for disease progression,causing deterioration of renal function up to renal failure,and is associated with an increased risk of end-stage renal disease and cardiovascular disease.Podocyte is one of the important components of the glomerular filtration barrier,and podocyte injury is the main cause of proteinuria.Autophagy,as an important mechanism to maintain podocyte homeostasis,is closely related to the nutritional status in vivo.Dagliflozin is a sodium-glucose cotransporter 2 inhibitor with nephroprotective effects,which has been shown to mimic the state of nutritional deprivation by inhibiting mammalian target of rapamycin 1 and activating amp-activated protein kinase and silent information regulator 1,thereby enhancing podocyte autophagy and reducing proteinuria.This article provides a systematic review on the role of dagliflozin in promoting podocyte autophagy in diabetic kidney disease through the nutrient-sensing signaling pathway and thus protecting renal function,so as to provide feasible clinical applications and future research recommendations for the prevention and treatment of diabetic kidney disease.