急性肾损伤每年导致全球超过200万人死亡。急性肾损伤不但可自身发展为终末期肾衰竭，还可促使慢性肾病加速形成终末期肾衰竭。目前对急性肾衰竭的治疗仅限于肾透析和肾移植，缺乏有效治疗手段。肾脏缺血再灌注损伤是导致急性肾损伤的最主要因素，申请人前期首次报道脂肪因子Apelin对缺血再灌注损伤引起的急性肾损伤有着良好的保护作用。但对于Apelin在肾脏缺血再灌注损伤中是如何在分子水平发挥各种保护功能还有待深入研究。本项目将在上述研究基础上，探索Apelin在急性肾脏缺血再灌注损伤模型中，对组蛋白甲基化和DNA去甲基化、炎症等通路的调节作用，扩展研究Apelin对脂多糖、阿霉素等诱导的肾毒性急性肾损伤是否具有保护作用，确认Apelin在急性肾损伤模型中的作用机制和作用靶点。本项目有望进一步阐明急性肾损伤的发病机制，并为其治疗提供新视角和理论依据。

Each year, acute renal injury leads to more than 2 million death worldwide. Acute renal injury not only can develop itself, but also can accelerate the development of chronic renal disease to end stage renal failure. Presently, the treatments for acute renal failure heavily rely on renal dialysis and renal transplantation, while effective treatments remain to be investigated. Previously, the applicant reported for the first time that the adipokine apelin shows protective effect against ischemia/reperfusion induced acute renal injury. Based on the results referred above, this proposal intends to study the effect that apelin has on LPS- and ADM-induced nephrotoxic acute kidney injury, and elucidate the regulation of apelin on histone methylation, DNA demethylation and inflammation in acute renal injury cells and animal models. These work shall help clarifying the mechanism and target of apelin in acute renal injury, elucidating the pathogenesis of acute renal injury and providing new angles for its treatment.