自噬在非酒精性脂肪性肝病发生发展中的作用

Role of autophagy in the occurrence and development of Non-alcoholic fatty liver disease

非酒精性脂肪性肝病(NAFLD)是以弥漫性肝细胞脂肪变性为主要特征的临床病理综合征,包括单纯性脂肪性肝病以及由其演变的脂肪性肝炎、脂肪性肝纤维化和肝硬化。原有的“两次打击”学说不能完全解释其发病机制,涉及多种因素的多重打击学说提供了更全面的描述,包括脂质毒性、炎症反应、纤维化和基因表达改变。自噬是溶酶体对胞浆成分降解的一种代谢途径。自噬参与该病多种发病机制,导致细胞脂质堆积、炎症反应和纤维化。本篇综述总结了Unc-51样自噬激活激酶1、腺苷酸激活蛋白酶、哺乳动物雷帕霉素复合物1与自噬的关系,并详细描述了自噬如何参与非酒精性脂肪性肝病的发生发展。

Non-alcoholic fatty liver disease(NAFLD)is a clinicopathological syndrome characterized by diffuse hepatocyte steatosis,including simple fatty liver disease and its evolution of steatohepatitis,fatty liver fibrosis and cirrhosis.The original"two-blow"theory cannot fully explain its pathogenesis,and the multiple-blow theory involving a variety of factors provides a more comprehensive description,including lipid toxicity,inflammation,fibrosis and changes in gene expression.Autophagy is a metabolic pathway for lysosome to degrade cytoplasmic components,which is involved in a variety of pathogenesis of the disease,leading to cellular lipid accumulation,inflammation and fibrosis.This review summarizes the relationship between Unc-51 like autophagy activating kinase 1(ULK1),AMP-activated protein kinase(AMPK),mammalian target of rapamycin complex 1(mTORC1)and autophagy,and describes in detail how autophagy participates in the occurrence and development of non-alcoholic fatty liver disease.