非酒精性脂肪性肝病发病机制研究进展——聚焦“巨噬细胞及其分子机制”

Research Progress in Pathogenesis of Nonalcoholic Fatty Liver Disease-Focusing on "Macrophages and Related Molecular Mechanisms"

非酒精性脂肪性肝病(NAFLD)是代谢综合征在肝脏的表现,其发病率逐年升高。阐明NAFLD的发病机制对其防治至关重要。然而,NAFLD的发病机制尚不完全清楚,“多重打击”学说是目前被普遍接受的发病机制。随着肝病免疫学的研究发展,巨噬细胞在“多重打击”学说中的重要地位不容忽视。从巨噬细胞来源角度讲,肝脏固有的和单核细胞来源的巨噬细胞都参与NAFLD的进展;从细胞功能角度讲,M1和M2型巨噬细胞分别在NAFLD时肝脏炎症和纤维化的进展中扮演不同的角色。此外,模式识别受体、补体激活和干扰素基因激活蛋白相关信号通路是巨噬细胞参与NAFLD发生发展的主要分子机制。

Nonalcoholic fatty liver disease(NAFLD)is recognized as the liver disease component of metabolic syndrome,and its incidence is increasing gradually.It is crucial to elucidate the pathogenesis of NAFLD for its prevention and treatment.However,the pathogenesis of NAFLD is still not completely clear,although the"multiple strikes"theory is now widely accepted.Along with the development of liver immunology,the important role of macrophages in"multiple strikes"theory cannot be ignored.From the source of macrophages,liver-resident macrophages and monocyte-derived macrophages are both involved in NAFLD progression.From the function of macrophages,M1 and M2 macrophages play important roles in the progression of liver inflammation and fibrosis of NAFLD,respectively.In addition,pattern recognition receptors,complement activation and interferon gene activating protein-related signaling pathways are the main molecular mechanisms for macrophages in the development of NAFLD.