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SIRT6在非酒精性脂肪性肝炎中的作用

敬贤丹^*, 唐琴, 何金汗

四川大学华西医院临床药学与药品不良反应研究室，成都 610041

摘要

SIRT6是沉默信息调节蛋白家族中的一员，具有烟酰胺腺嘌呤二核苷酸依赖的组蛋白去乙酰化酶活性和单ADP-核糖基转移酶活性。SIRT6在机体关键的生理和病理过程中起着重要作用，包括脂代谢、炎症、氧化应激以及纤维化等，被认为是代谢综合征的潜在治疗靶点。SIRT6敲除小鼠表现出严重的脂肪肝，非酒精性脂肪性肝炎(nonalcoholic steatohepatitis, NASH)小鼠模型的肝组织中SIRT6的表达量明显低于正常小鼠，而过表达SIRT6能显著减轻NASH所引起的肝损伤，提示SIRT6可能具有保护NASH动物模型的作用。本文将重点综述SIRT6在NASH发生、发展过程中的重要调节作用。

关键词： SIRT6; 非酒精性脂肪性肝炎; 脂代谢; 炎症; 肝纤维化

分类号：R58

The role of SIRT6 in nonalcoholic steatohepatitis

JING Xian-Dan^*, TANG Qin, HE Jin-Han

Laboratory of Clinical Pharmacy and Adverse Drug Reaction, West China Hospital, Sichuan University, Chengdu 610041, China

Abstract

SIRT6, a member of the silencing information regulatory protein family, is a nicotinamide adenine dinucleotide-dependent histone deacetylase and an ADP-ribose transferase enzyme. It plays an important role in fundamental physiological and pathological processes, including lipid metabolism, inflammation, oxidative stress and fibrosis, and is considered as a potential therapeutic target for metabolic syndrome. SIRT6 knockout mice displayed severe fatty liver, and the expression of SIRT6 in the liver of nonalcoholic steatohepatitis (NASH) mice was significantly lower than that of normal mice. Overexpression of SIRT6 significantly ameliorated NASH-induced liver damage. It is suggested that SIRT6 may play a key role in protecting against NASH. In this paper, we review the important regulatory functions of SIRT6 in the occurrence and development of NASH.

Key words: SIRT6; nonalcoholic steatohepatitis; lipid metabolism; inflammation; liver fibrosis

收稿日期：2021-01-20　　录用日期：2021-07-16

通讯作者：敬贤丹　　E-mail: jinhanhe@scu.edu.cn

DOI: 10.13294/j.aps.2021.0074

引用本文：

敬贤丹, 唐琴, 何金汗. SIRT6在非酒精性脂肪性肝炎中的作用[J]. 生理学报 2021; 73 (5): 745-754.

JING Xian-Dan, TANG Qin, HE Jin-Han. The role of SIRT6 in nonalcoholic steatohepatitis. Acta Physiol Sin 2021; 73 (5): 745-754 (in Chinese with English abstract).