PDF(Pubmed)
Abstract：
Ethanol consumption triggers oxidative stress by generating reactive oxygen species (ROS) through its metabolites. This process leads to steatosis and liver inflammation, which are critical for the development of alcoholic liver disease (ALD). Autophagy is a regulated dynamic process that sequesters damaged and excess cytoplasmic organelles for lysosomal degradation and may counteract the harmful effects of ROS-induced oxidative stress. These effects include hepatotoxicity, mitochondrial damage, steatosis, endoplasmic reticulum stress, inflammation, and iron overload. In liver diseases, particularly ALD, macroautophagy has been implicated as a protective mechanism in hepatocytes, although it does not appear to play the same role in stellate cells. Beyond the liver, autophagy may also mitigate the harmful effects of alcohol on other organs, thereby providing an additional layer of protection against ALD. This protective potential is further supported by studies showing that drugs that interact with autophagy, such as rapamycin, can prevent ALD development in animal models. This systematic review presents a comprehensive analysis of the literature, focusing on the role of autophagy in oxidative stress regulation, its involvement in organ-organ crosstalk relevant to ALD, and the potential of autophagy-targeting therapeutic strategies.
摘要：
乙醇消耗通过其代谢物产生活性氧（ROS）来触发氧化应激。这个过程导致脂肪变性和肝脏炎症，这对酒精性肝病（ALD）的发展至关重要。自噬是一个受调节的动态过程，可隔离受损和过量的细胞质细胞器以进行溶酶体降解，并可能抵消ROS诱导的氧化应激的有害影响。这些影响包括肝毒性，线粒体损伤，脂肪变性,内质网应激,炎症,铁过载。在肝脏疾病中，特别是ALD，巨自噬被认为是肝细胞的保护机制，尽管它在星状细胞中似乎没有发挥相同的作用。在肝脏之外，自噬还可以减轻酒精对其他器官的有害影响，从而提供防止ALD的附加保护层。研究表明，与自噬相互作用的药物，如雷帕霉素，在动物模型中可以预防ALD的发展。这篇系统的综述对文献进行了全面的分析，关注自噬在氧化应激调节中的作用，它参与与ALD相关的器官-器官串扰，以及自噬靶向治疗策略的潜力。
