外周时钟基因在非酒精性脂肪性肝炎发展与防治中的作用
Role of peripheral clock genes in the progression,prevention,and treatment of nonalcoholic steatohepatitis
刘思言 1田静怡 1黄雨扬 1谷天麒 1邓茗月 1杨攀2
作者信息
- 1. 重庆医科大学国际医学院,重庆 401331
- 2. 重庆医科大学附属第二医院急救部,重庆 400000
- 折叠
摘要
非酒精性脂肪性肝炎(NASH)作为非酒精性脂肪性肝病的严重临床表现形式,以肝脂质沉积、炎症损伤为特征.目前NASH的临床治疗药物仍处于探索实验阶段,亟待取得进展.有研究指出NASH的发病机制与肝脏昼夜节律紊乱有关,具体可表现为肝时钟基因如BMAL1等表达失调,导致肝内脂质生成增多、脂肪酸氧化减少以及促炎症因子激活.因此,改善肝脏昼夜节律,调节肝时钟基因表达被视为防治NASH的可行策略.目前已有通过激活时钟基因编码蛋白治疗NASH的药物应用于动物实验,如REVERB全激动剂SR9009,其能抑制肝脏的炎症发展,有效证实了靶向时钟编码蛋白在NASH治疗中的可能性.本文总结了肝时钟基因在调节肝脂质代谢与炎症发生发展中的作用,阐述了近年来以时钟基因及其相关蛋白作为靶点的药物研究进展,以期为NASH治疗提供新靶点.
Abstract
As a severe clinical manifestation of nonalcoholic fatty liver disease,nonalcoholic steatohepatitis(NASH)is characterized by lipid deposition and inflammatory damage in the liver.At present,clinical medications for NASH are still in the exploratory phase,and it is urgent to make progress.Recent studies have shown that the pathogenesis of NASH is associated with circadian rhythm disorders in the liver,with the specific manifestation of dysregulated expression of liver clock genes such as BMAL1,which increases hepatic lipogenesis,reduces fatty acid oxidation,and activates pro-inflammatory factors.Therefore,improving circadian rhythm of the liver and regulating the expression of liver clock genes are feasible strategies for the prevention and treatment of NASH.Currently,some medications for NASH via activating the proteins encoded by clock genes have been applied in animal experiments,for example,the REVERB full-agonist SR9009 can inhibit the development of liver inflammation,which confirms the possibility of NASH treatment by targeting the proteins encoded by clock genes.This article summarizes the role of hepatic clock genes in regulating lipid metabolism and the development and progression of inflammation in the liver and elaborates on the recent advances in medications targeting clock genes and the proteins encoded by clock genes,in order to provide new targets for the treatment of NASH.
关键词
非酒精性脂肪性肝病/昼夜节律/时钟蛋白质类Key words
Non-alcoholic Fatty Liver Disease/Circadian Rhythm/CLOCK Proteins引用本文复制引用
出版年
2024
国家科技期刊平台
NSTL
万方数据