肾小球足细胞损伤是蛋白尿形成及肾脏疾病进展的重要原因之一，研究发现，足细胞损伤同时伴随异常线粒体累积、线粒体功能障碍和/或细胞自噬异常，但机制尚未完全明确。并有报道，PINK1/Parkin通路是介导线粒体自噬的经典信号通路，且PINK1蛋白作为Parkin蛋白的上游分子调控该信号通路。我们假设，PINK1/Parkin介导的线粒体自噬障碍可能是足细胞损伤的机制之一。为证实这一假说，我们建立足细胞损伤模型，通过micro RNA干扰技术沉默pink1和parkin基因，观察足细胞线粒体损伤程度、自噬相关蛋白LC3和Beclin-1的mRNA、蛋白和分布的变化；观察PINK1/Parkin信号通路与自噬相关蛋白LC3和Beclin-1的相互作用，研究PINK1/Parkin介导的线粒体自噬功能障碍在足细胞损伤中的作用机制，阐明线粒体自噬对足细胞结构功能的稳态作用，为防治蛋白尿提供新的措施。

Glomerular podocyte injury is one of the important reasons of proteinuria and progression of renal diseases.Studies manifested that glomerular podocyte was damaged along with accumulation of abnomal mitochondria,mitochondria dysfunction and/or disturbance of cellular autophagy,of which mechanism is still unclear. Researches also reported that PINK1/Parkin pathway was a classical signaling pathway in mediating mitochondria autophagy(mitophagy),in which PINK1 was the upstream protein to recruit Parkin.We hypothesize that PINK1 / Parkin mediated mitophagy dysfunction one of the mechanisms of podocyte injury.To prove this hypothesis, we establish podocyte damage model, silence pink and parkin gene by micro RNA interference technology,observe the impaired degree of mitochondria in damaged podocyte, the changes of autophagy related protein LC3 and Beclin-1 mRNA, proteinand distribution,at the meanwhile, observe the interaction between PINK1/Parkin pathway and autophagy related protein LC3 , Beclin-1.Our Objectives is to clarify the influence of mitophagy to podocyte homeostasis by studying the mechanism of dysfunction of PINK1 / Parkin mediated mitophagy in damaged podocyte,which is greatly helpful for searching new solutions preventing and treating proteinuria.