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酒精性肝病:对肝病发病机制的新认识。

Alcoholic liver disease: a new insight into the pathogenesis of liver disease.

机构信息

College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea.

Department of Internal Medicine, Korea University Medical Center, Seoul, Republic of Korea.

出版信息

Arch Pharm Res. 2022 Jul;45(7):447-459. doi: 10.1007/s12272-022-01392-4. Epub 2022 Jun 27.

Abstract

Excessive alcohol consumption contributes to a broad clinical spectrum of liver diseases, from simple steatosis to end-stage hepatocellular carcinoma. The liver is the primary organ that metabolizes ingested alcohol and is exquisitely sensitive to alcohol intake. Alcohol metabolism is classified into two pathways: oxidative and non-oxidative alcohol metabolism. Both oxidative and non-oxidative alcohol metabolisms and their metabolites have toxic consequences for multiple organs, including the liver, adipose tissue, intestine, and pancreas. Although many studies have focused on the effects of oxidative alcohol metabolites on liver damage, the importance of non-oxidative alcohol metabolites in cellular damage has also been discovered. Furthermore, extrahepatic alcohol effects are crucial for providing additional information necessary for the progression of alcoholic liver disease. Therefore, studying the effects of alcohol-producing metabolites and interorgan crosstalk between the liver and peripheral organs that express ethanol-metabolizing enzymes will facilitate a comprehensive understanding of the pathogenesis of alcoholic liver disease. This review focuses on alcohol-metabolite-associated hepatotoxicity due to oxidative and non-oxidative alcohol metabolites and the role of interorgan crosstalk in alcoholic liver disease pathogenesis.

摘要

过量饮酒可导致广泛的肝脏疾病谱,从轻症脂肪变性到终末期肝细胞癌。肝脏是代谢摄入酒精的主要器官,对酒精摄入极为敏感。酒精代谢分为两种途径:氧化和非氧化酒精代谢。氧化和非氧化酒精代谢及其代谢产物对包括肝脏、脂肪组织、肠道和胰腺在内的多个器官都具有毒性作用。尽管许多研究都集中在氧化酒精代谢物对肝脏损伤的影响上,但非氧化酒精代谢物在细胞损伤中的重要性也已被发现。此外,肝外酒精作用对于提供酒精性肝病进展所需的额外信息至关重要。因此,研究产生酒精的代谢物以及肝脏和表达乙醇代谢酶的外周器官之间的器官间串扰,将有助于全面了解酒精性肝病的发病机制。本文重点介绍了氧化和非氧化酒精代谢物相关的酒精代谢物相关性肝毒性,以及器官间串扰在酒精性肝病发病机制中的作用。

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