缺血再灌注(IR)损伤是影响移植肾功能的重要因素。肾小管上皮细胞是肾IR损伤的主要效应细胞。PPARα在多种肾小管上皮细胞相关肾损伤中起重要保护作用。我们预实验发现PPARα激动剂非诺贝特预处理可以减轻小鼠肾IR损伤，同时伴随氧化应激、凋亡及炎症反应的降低。我们还发现PPARα可以增强SK1/S1P通路的表达及自噬水平，而阻断该通路可以逆转非诺贝特的保护作用。根据预实验结果和文献研究，我们推测激动PPARα可上调SK1/S1P的表达，增强自噬水平进而起肾保护作用。在该过程中，PPARα和SK1的调控关系及对自噬的影响还需要进一步的研究。人源性肾小管上皮细胞系HK-2和小鼠原代肾小管上皮细胞体外实验有助于进一步确认PPARα对SK1/S1P通路的调控作用及保护肾IR损伤的机制。本研究将可能揭示PPARα调控应激状态下自噬和细胞生存的新机制，并为肾IR损伤及其他相关肾病提供新的治疗干预靶点。

Ischemic reperfusion (IR) injury is one of the leading causes of renal dysfunction post kidney transplantation. Renal tubular epithelial cell injury plays important role in the development of IR injury. PPARα have reportedly could protect against various renal injuries associated renal tubular epithelial cell damage. Our preliminary experiment found that activation of PPARα by its ligand attenuated renal IR injury in accompany with decreased levels of oxidative stress, apoptosis and immune response. Moreover, activation of PPARα up-regulated the levels of SK1/S1P and autophagy. The protective effect of PPARα activation was markedly attenuated by blocking SK1/S1P pathway or autophagy. Based on these findings, we hypothesize that PPARα is a key regulator of autophagy in the kidney, thereby compromising the defense mechanisms of renal IR injury via promoting SK1/SIP autophagy pathway. In vivo study using primary tubular epithelial cells is neccesary to prove this theory . These studies may help to facilitate understanding of the role of PPARα in autophagy and renal IR injury, which may serve as a novel therapeutic target