于馨洋　邵宁匡　洪宇

[摘要] 非酒精性脂肪性肝病（NAFLD）是肝脏疾病进展，2型糖尿病（T2DM）、心血管疾病的独立危险因素。T2DM与NAFLD具有共同发病机制而常合并出现。肝脏脂肪蓄积和线粒体功能障碍是T2DM合并NAFLD发病机制的重要环节。肝细胞脂质自噬介导的脂代谢调节与线粒体自噬介导的线粒体质量调控是疾病治疗的潜在靶点。然而，自噬被认为是一把双刃剑，在疾病发展中自噬活性动态变化，适度自噬介导肝脏保护，但过度和衰竭的自噬加重肝脏损伤。自噬在疾病中的动态调控机制亟待阐明。本文旨在探讨调节自噬对T2DM合并NAFLD治疗的潜在价值，以期为疾病防治提供新靶向。

[关键词] 非酒精性脂肪性肝病；2型糖尿病；脂质自噬；线粒体自噬

[中图分类号] R58 [文献标识码] A [文章编号] 1673-7210（2017）05（c）-0043-04

[Abstract] Non-alcoholic fatty liver disease （NAFLD） is an independent risk factor for advanced liver disease， type 2 diabetes mellitus （T2DM）， and cardiovascular diseases. T2DM is always accompanied by NAFLD as result of a common pathogenesis. Hepatic lipid accumulation and mitochondrial dysfunction proved to be two essential mechanisms for the pathogenesis of T2DM with NAFLD. Regulation of lipophagy and mitophagy in hepatocyte are potential targets for disease therapy. However， autophagy is considered to be a double-edged sword. Moderate autophagy protects liver， yet excessive or failure one aggravates its injury. The evolution of NAFLD could be associated with dynamic regulation of autophagy and additional studies are required. This review aims to investigate the potential value of autophagy regulation in the treatment of NAFLD in type 2 diabetes mellitus， in order to provide innovative targets for therapeutic intervention.

[Key words] Non-alcoholic fatty liver disease； Type 2 diabetes mellitus； Lipophagy； Mitophagy

非酒精性脂肪性肝病（non-alcoholic fatty liver disease，NAFLD）是一种与胰岛素抵抗（IR）、脂质代谢紊乱、慢性炎症以及遗传易感性密切相关的获得性代谢应激性肝损伤，疾病谱包括单纯性脂肪肝、脂肪性肝炎（steatohepatitis，NASH）及其相关纤维化、肝硬化[1]。NAFLD是肝脏疾病进展，2型糖尿病（type 2 diabetes mellitus，T2DM）、心血管疾病的独立危险因素[2]。T2DM与NAFLD因具有共同发病机制而常伴随发生。总人群中NAFLD发病率达20%～30%，T2DM人群中脂肪肝发病率高达60%～80%[3]。T2DM合并NAFLD发生，进一步恶化糖代谢，增加NASH发病风险，加速向肝硬化、肝癌进展，形成恶性循环，最终导致严重糖代谢紊乱和不良肝病结局。研究表明，肝脏脂肪蓄积和线粒体功能障碍是T2DM合并NAFLD发病机制的重要环节[4]。自噬是细胞实现自身代谢需要和细胞器更新的重要机制。……