非酒精性脂肪性肝病发病机制的研究进展

非酒精性脂肪性肝病（NAFLD）是指与过量饮酒无关的临床综合征,主要病理改变包括肝细胞弥漫性脂肪变性和脂肪堆积。NAFLD动物模型表现出显著的肝脏微循环障碍,关于其形成机制,被广为接受的为＂二次打击＂学说。该学说认为肥胖、胰岛素抵抗等因素作为＂第一次打击＂,导致肝脏中脂质堆积,形成单纯性脂肪肝,增加了＂第二次打击＂造成的肝脏损伤的易感性,这些因素包括炎症、枯否细胞功能障碍、氧化应激、线粒体障碍、脂肪因子调节紊乱等,导致非酒精性脂肪性肝炎甚至纤维化等更严重疾病的发生。

Advances in pathogenesis of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease（NAFLD）,a clinical syndrome unrelated to excessive alcohol intake,is char-acterized by diffuse fatty degeneration of liver cells and fat accumulation.Animal models of NAFLD exhibit obvious hepatic mi-crocirculation dysfunction.The widely accepted pathogenesis of NAFLD was based on ′2-hit hypothesis′.Obesity and insulin re-sistance as the ′first-hit′ lead to hepatic triglyceride accumulation or steatosis,increase susceptibility of the liver to injury me-diated by ′second-hit′,such as inflammation,Kupffer cell dysfunction,mitochondrial dysfunction,oxidative stress,and adipokines adjustment disorders,which in turn lead to steatohepatitis,even fibrosis.