肝缺血再灌注损伤（HIRI）常导致术后肝功能不全并直接影响患者预后，目前尚无有效防治手段。氧化应激损伤是HIRI的关键机制，申请人既往研究发现HIRI致肝细胞氧化应激损伤，活性氧（ROS）在细胞内蓄积，应用抗氧化剂效果不明显，MG53修复细胞膜却有明显的保护作用。进一步预实验发现ROS堆积致肝细胞发生Ferroptosis，补充MG53重组蛋白可减轻Ferroptosis，同时检测到此过程MG53与陷窝蛋白Caveolin-1结合紧密，抑制Caveolin-1削弱了其保护作用。据此本项目提出“MG53/Caveolin-1细胞膜修复复合体通过调控肝细胞Ferroptosis减轻HIRI损伤”的假说。拟通过TAT-MG53融合蛋白、在体敲减小鼠MG53蛋白等技术，构建小鼠HIRI模型及肝细胞缺氧复氧模型，从膜修复角度探讨防治HIRI的机制，为遏制HIRI后肝细胞损伤提供理论依据及新的靶点。

Hepatic ischemia-reperfusion injury (HIRI) often leads to postoperative liver dysfunction and directly affects the prognosis of patients，which has no effective prevention and treatment. Oxidative stress injury plays a dominant role in HIRI. Applicant have found that HIRI-induced oxidative stress injury and reactive oxygen species (ROS) accumulation in hepatocyte. Although the protective effects of antioxidants are not obvious, MG53 has obvious protective effects on repairing cytomembrane. In pre-experiment, we further found that ROS accumulation caused hepatocyte Ferroptosis, MG53 and CAV-1 formed a cytomembrane-repair complex to reduce Ferroptosis, which suggesting that repairing cytomembrane damage and blocking Ferroptosis caused by ROS accumulation become the main point of HIRI prevention and treatment. According to this project, we hypothesize that "MG53/CAV-1 cytomembrane-repair complex alleviate HIRI by regulating hepatocyte Ferroptosis". The mouse HIRI model and hepatocyte hypoxia-reoxygenation model were constructed by TAT-MG53 fusion protein technology and in vivo knockdown of mouse MG53 protein technology. The mechanism of prevention and treatment of HIRI will be studied from the perspective of membrane repair. It will provide a new theoretical basis and targets.