PGC-1α在糖尿病肾病发病中的作用及分子机制

过氧化物酶体增殖活化受体γ辅助活化因子1α (PGC-1α) 对于脂类和葡萄糖代谢以及氧化应激具有重要的调节作用。目前，PGC-1α在糖尿病肾病发病中的作用还不清楚。本研究将利用基因转染、siRNA干扰等分子生物学技术观察高糖对PGC-1α表达的影响以及PGC-1α与高糖状态下肾小管细胞脂质沉积、凋亡和表型转化的关系；探讨高糖对肾小管细胞PGC-1α表达的上游调控分子和信号通路以及PGC-1α的下游作用分子。为了探讨SIRT1-PGC-1α在糖尿病肾病中的作用，本项目将观察去乙酰化酶SIRT1激活剂(SRT1720)和抑制剂（EX527）对糖尿病动物(db/db 小鼠)肾脏病变的作用和PGC-1α表达的影响以及相关分子机制。本研究将有助于揭示PGC-1α在糖尿病肾病发病中的作用和分子机制，为糖尿病肾病防治提供新的作用靶点和思路，具有重要的理论意义和实用价值。

Peroxisome proliferator-activated receptor (PPAR)? co-activator 1α (PGC-1α) plays key roles in the regulation of lipid and glucose homeostasis, and in the control of oxidative stress. At present, the role of PGC-1α in diabetic nephropathy is unknown. In this project, we will investigate the effect of high glucose on expression of PGC-1α and the effect of PGC-1α on high-induced lipogenesis, apoptosis and epithelial-mesenchymal transition in renal tubular cells using gene transfection, siRNA interference and other molecular biology techniques. To explores the upstream effectors and signal transduction pathways in high-induced expression of PGC-1α and the downstream effectors of PGC-1α in renal tubular cells. In order to explore the effects of SIRT1- PGC-1α on diabetic nephropathy, we will investigate the role and moleculor mechanism of SRT1720 (SIRT1 activator) and EX527 (SIRT1 inhibitor) on renal pathological changes and expression of PGC-1α in type 2 diabetic mice kidney. This project will be helpful to reveal the role and molecular mechanisms of PGC-1α in diabetic nephropathy. And this project has important theory significance and practical value for offering a new therapeutic strategies for the prevention and treatment of diabetic nephropathy.