肾脏缺血再灌注（IRI）导致的急性肾损伤发病率和死亡率都很高，尚缺乏有效的防治手段。肾小管上皮细胞死亡是肾脏IRI所引起的最主要的病理改变形式，因此深入研究上皮细胞死亡机制是阐明肾脏IRI发病机理的有效途径。故本项目拟研究细胞坏死在肾脏缺血再灌注损伤导致的肾脏损伤的不同阶段中存在的类型及其作用。首先，利用C57BL/6小鼠构建肾脏IRI模型，分析在不同的肾脏损伤阶段存在的细胞坏死种类。其次，利用肾脏上皮细胞特异性敲除ACSL4基因小鼠、肾脏上皮细胞及铁坏死抑制剂，筛选相关的信号通路，阐明铁坏死在不同肾脏损伤阶段中的作用；最后，利用肾脏上皮细胞特异性敲除MLKL基因小鼠、肾脏上皮细胞及细胞程序性坏死抑制剂，筛选相关的信号通路，阐明细胞程序性坏死在不同肾脏损伤阶段中的作用。本项目的完成将为临床治疗肾脏IRI引起的急性肾损伤提供新思路。

Acute kidney injury (AKI) is a common clinical condition with considerable morbidity and mortality in humans. Renal ischemia reperfusion injury (IRI) is the main cause of AKI. But there is no effective therapy for this devastating clinical condition. Renal tubular epithelial cell death is the most important pathological change caused by renal IRI. Therefore, to deeply study the mechanism of cell death is an effective way to clarify the pathogenesis of renal IRI. The types and roles of cell necrosis in renal IRI will be studied in this project. First, we will perform renal IRI on C57BL/6 mice to analyze the types of cell necrosis in renal IRI. Second, we will use renal tubular specific ACSL4 knockout mice and renal tubular epithelial cells to study the roles of ferroptosis in renal IRI. Third, we will use renal tubular specific MLKL knockout mice and renal tubular epithelial cells to study the roles of necroptosis in renal IRI. This study will reveal a novel strategy for renal IRI.