足细胞自噬调控在肝细胞生长因子保护糖尿病肾病中作用机制的实验研究

自噬是肾脏足细胞在生理和病理情况下，赖以维持细胞内环境稳态和应对各种损伤应激的重要生存调节机制之一。自噬不济会导致足细胞内严重的氧化应激。氧化应激作为糖尿病及其并发症的共同病理机制之一，可通过多种途径介导高血糖对足细胞的损伤。足细胞损伤在糖尿病肾病（DN）的发病机制中占有非常重要的始动地位，且贯穿DN发生发展的始终。肝细胞生长因子（HGF）对肾脏具有良好的营养保护作用。基于我们的前期研究发现：HGF可抑制高糖刺激下的大鼠系膜细胞内的氧化应激，本项目拟通过体内外研究观察HGF对高糖环境下足细胞内自噬和氧化应激的影响，探讨足细胞自噬调控在HGF防治DN中发挥的作用及其与HGF抗氧化效应的联系，并阐明这些作用涉及的信号通路及互相之间的影响机制（Cross Talk），以明确HGF调控足细胞自噬的机理，完善HGF的抗氧化机制和HGF保护肾脏的机制，为糖尿病肾病的治疗研究提供新的思路和实验依据。

Autophagy is an essential mechanism to maintain podocyte homeostasis under physiological and pathological conditions. Impaired autophagy led to severe oxidative stress in podocytes. Oxidative stress, a common pathogenetic mechanism underlying diabetes and its complications, mediates high glucose-induced podocyte injury via multiple pathways. Podocyte injury is a key initial event in pathogenesis of diabetic nephropathy (DN) and presented in all the stages of development of DN. Hepatocyte growth factor (HGF) is a putative renotrophic and renoprotective factor. In the previous study, we found that HGF could prevent high glucose-induced oxidative stress in rat mesangial cells. Next, in this project, we want to investigate how HGF affects autophagy and oxidative stress in high glucose-stimulated podocytes, explore the involved signal pathways, and elucidate the cross talk among these signaling. These should help in revealing the mechanism of HGF to regulate autophagy in podocytes as well as to function as an antioxidant and protective factor in kidney, thus providing novel insights into therapeutic approaches for the treatment of diabetic nephropathy.