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 characterized by diffuse fatty degeneration of liver cells and fat accumulation. Animal models of NAFLD exhibit obvious hepatic microcirculation dysfunction. The widely accepted pathogenesis of NAFLD was based on ′2-hit hypothesis′. Obesity and insulin resistance as the ′first-hit′ lead to hepatic triglyceride accumulation or steatosis. increase susceptibility of the liver to injury mediated 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 .