靶向自噬治疗2型糖尿病合并非酒精性脂肪性肝病的机制研究

Mechanism research on targeted autophagy therapy of non-alcoholic fatty liver disease in type 2 diabetes mellitus

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。

Non-alcoholic fatty liver disease （NAFLD） is an independent risk factor for advanced liver disease, type 2 di- abetes mellltus （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.