肝移植是拯救终末期肝病最有效的手段，然而肝移植等候者因供肝短缺而死亡的概率逐年增加，导致边缘供肝逐渐纳入选择范围，其中中重度脂肪肝比例最高。我们前期在人和大鼠脂肪肝肝移植的研究中发现脂肪供肝对冷缺血保存极为敏感，供肝获取后冷保存时间延长会直接造成脂肪供肝的不可逆损伤，导致术后早期移植物功能不全，受体和移植物累计生存率下降。常温离体灌注系统为脂肪供肝提供氧和能量，维持肝细胞的有氧代谢，并具有移植前预处理的潜能。本课题拟利用常温灌注平台，在灌注液中加入二碘化甲状腺氨酸药物脱脂进行预处理，经过短时间的修复治疗，逐步将细胞内的脂质分解并排出，有效逆转供肝脂肪变，并在猪肝移植模型上，评估在体移植的生存率。通过离体灌注和氧自由基损伤实验，分析常温灌注系统对脂肪肝的修复作用中是否由PPARγ/ADRP脂滴信号通路介导。最终为临床合理保存和利用脂肪供肝，拓展供肝来源提供理论依据。

Liver transplantation is known to be the most effective way to save end-stage liver disease. The increasing waiting list mortality as a result of ongoing organ shortage has led to the use of organs from extended criteria of moderate to severe steatotic donor livers. Our previous study on human and rat steattotic liver transplant demonstrated that steatotic livers were susceptible to cold ischemia preservation, which is the critical factor rendering steatotic livers nonviable. The presence of severe steatosis is correlated with the development of graft initial poor function and involved recipient and graft survival. The aim of this research is to develop a normothermic perfusion/defatting system. Oxygen and metabolic substance are added to maintain cellular aerobic metabolism within a physiological environment in porcine steatotic liver model. Perfusate containing 3,5-L-diiodothyronine, an effective defatting agent, upregulates both lipid oxidation and export throughout a short perfusion period. Porcine liver transplantation model is planed using steatotic graft which is preconditioned by the defatting system, to make sure if the survival can be improved in vivo. To further study its mechanism, the gene and protein changes of PPARγ/ADRP droplet pathway during extracorporeal perfusion and hepatocyte H2O2 culture are tested. Consequently, normothermic perfusion/defatting system can reduce the degree of hepatic graft steatosis to a certain extent. By restoring function in marginal steatotic donor organs, the donor pool might be greatly expanded.