Kupffer细胞是肝内天然免疫和适应性免疫网络的关键调节细胞。在我们前期的研究中发现炎性活化的Kupffer细胞及其相关的肝内天然免疫紊乱在NAFLD发生、发展中具有重要作用。最近研究显示，巨噬细胞M1/M2型不同表型活化转变将影响机体炎症-代谢过程。已发现核受体PPARgamma在调控机体能量代谢、炎症免疫反应中具有重要地位，并参与巨噬细胞极化改变。因此，本研究拟通过动物模型及细胞实验观察体内外高脂环境对Kupffer细胞M1-M2极化的影响，并探索核受体PPARgamma在脂质诱导的Kupffer细胞M1/M2极化转变中的作用及调控机制，以及不同极化类型的Kupffer细胞对肝细胞脂质代谢的影响。从而阐明异常脂质对Kupffer细胞极化的影响,并设计基于调控Kupffer细胞极化为基础的治疗策略,为预防、治疗NAFLD提供新的理论依据和新视野。

Kupffer cell is the key cell who regulates the hepatic innate immune system and adaptive immune system.Our recent studies have shown that inflammatory activated Kupffer cell and its related abnormality of hepatic innate immune system were involved in the development of non-alcoholic fatty liver disease. Recent studies have shown that M1/M2 phenotype polarization of macrophages is thought to contribute to the progression of inflammation and metabolism. Nuclear receptor PPARgamma played important role in body engery metabolism and inflammatory immune response,and was also implicated in macrophages polarization. In the present study, effect of high lipid environment on M1/M2 phenotype polarization of Kupffer cell was observed through in vivo animal models and in vitro cell experiments. Furthermore,we investigate the role of nuclear receptor PPARgamma in the switch of Kupffer cell M1/M2 polarization induced by lipid , and explore the mechanism of such modulation. In addition,effect of the different phenotype polarization of Kupffer cells on lipid metabolism of hepatocytes was further investigated. Based on the present study, we want to elucidate the mechanism of lipid induced Kupffer cell polarization, and design a new therapeutic strategy based on modulation of Kupffer cell polarization to provide a new theoretical basis for NAFLD prevention and treatment.