自噬在酒精性肝病中的作用

Role of Autophagy in Alcoholic Liver Disease

酒精性肝病(alcoholic liver disease,ALD)是由于长期大量饮酒引起的慢性肝损伤,其发病机制极其复杂。目前研究认为,乙醇代谢及其一些相关代谢物,例如乙醛和活性氧等的产生,是造成肝细胞毒性的重要原因。由这些物质所引起的细胞氧化应激、炎症反应、线粒体损伤和脂代谢紊乱等是引起肝损伤的重要因素。迄今为止,临床上对于ALD仍然缺乏特效的治疗药物。因此,进一步了解ALD的发生发展机制,针对相关分子开发有效的靶向药物是亟待解决的问题。自噬是真核生物进化保守的一种溶酶体降解过程,通过清除有害的细胞器和大分子物质促进细胞新陈代谢,并维持细胞内环境稳态。众多的研究揭示,乙醇可通过多种途径干扰自噬过程进而加剧酒精性肝损伤。而自噬在ALD的发生发展中发挥重要调控作用,包括清除肝细胞中多余的脂滴和损伤的线粒体以及积累的蛋白质聚合物等。故活化自噬可一定程度上减轻ALD。虽然目前已有较多关于自噬及其与ALD关系的研究,但仍有许多关键问题尚未解决。本文将综述有关自噬及其参与ALD调控的研究进展,同时还将比较与分析不同ALD造模方式对自噬影响及其可能的因素。最后初步探讨基于自噬调控的ALD防治策略,以期为该病治疗提供新思路。

Alcoholic liver disease(ALD)is a chronic liver injury caused by long-term heavy drinking and its pathogenesis is extremely complex.It is believed that ethanol metabolism and the production of some related metabolites,such as acetaldehyde and reactive oxygen species,are the important causes of hepatotoxicity.Oxidative stress,inflammation,mitochondrial damage and lipid metabolism disorders caused by these substances are crucial factors that cause ALD.Oxidative stress,inflammatory response,mitochondrial injury and lipid metabolism disorder caused by these substances are important factors causing liver injury.So far,there is still a lack of effective therapeutic drugs for ALD.Therefore,it is an urgent problem to further understand the mechanism of the occurrence and development of ALD and to develop effective targeted drugs for related molecules.Autophagy is a lysosomal degradation process that is conservatively evolved in eukaryotes.It promotes cellular metabolism and maintains the homeostasis of the environment by removing detrimental organelles and macromolecular substances.Numerous researches have disclosed that ethanol can disturb the process of autophagy in a variety of ways to exacerbate alcoholic liver injury.However,autophagy plays a vital regulatory role in the development and progress of ALD,including removing excessive lipid droplets,damaged mitochondria and accumulated protein polymers from hepatocytes.Therefore,activation of autophagy may alleviate ALD to a certain extent.Although there have been many investigations on autophagy and its relationship with ALD,many key issues remain to be resolved.This article reviewed the research progress on autophagy and its participation in ALD regulation.At the same time,it also compared and analyzed the effects and potential causes of different ALD modeling methods on autophagy.Finally,we preliminarily discussed the prevention and treatment strategies of ALD based on autophagic regulation,which may provide new ideas for the treatment of this disease.