非酒精性脂肪性肝病（NAFLD）的特征性表现是肝细胞内过量的脂滴沉积，新近发现细胞自噬可以有效地吞噬细胞中的脂滴、降解脂质。研究显示脂质代谢的关键因子固醇调节元件结合蛋白-2（SREBP-2）能激活肿瘤细胞中的自噬途径，在肝细胞中是否也有同样的作用目前未见报道，此外，SREBP-2在肝细胞中如何促进自噬，是通过单个抑或多个功能结构域来影响脂质自噬目前尚不明确。因此，本课题以SREBP-2做为切入点，通过采用NAFLD动物及细胞模型，结合基因敲除及酶学技术，明确SREBP-2蛋白与细胞自噬的内在联系，利用分子生物学方法调节肝细胞内SREBP-2蛋白片段的表达、增加自噬相关蛋白的分泌，达到促进脂质自噬的目的，为临床诊治NAFLD提供新的理论和实验依据。

Excessive hepatic lipid accumulation is the characteristic manifestation of Nonalcoholic fatty liver disease (NAFLD). Emerging evidence indicates that lipid droplets can be effectively phagocytosed and degradated by autophagy. As an key factor of lipid metabolism, sterol regulatory element binding protein-2 (SREBP-2) activates autophagy in Hela cells, but no publications suggest in hepatocytes, and which protein domain acts in this function is still unknown. Therefore, this project is to confirm that SREBP-2 activates autophagy to regulate hepatic lipid metabolism by lipophagy and which kinds of protein domain relates to it, through animal and cell model of NAFLD, and molecular biology tools to regulate the expressions of SREBP-2 protein in hepatocytes. At the same time, we could increase the secretion of autophagy related proteins and promote the lipophagy. Our project is due to provide new theoretical and experimental basis for clinical diagnosis and therapy of NAFLD.