表观遗传修饰在酒精性肝病长期进展中的作用研究进展  

Research advances on the role of epigenetic modifications in the long-term progression of alcoholic liver disease

作　　者：高寒 肖大可 王伽伯 马志涛 GAO Han;XIAO Da-ke;WANG Jia-bo;MA Zhi-tao(School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;College of Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China)

机构地区：[1]福建中医药大学药学院,福建福州350122 [2]首都医科大学中医药学院,北京100069

出　　处：《药学学报》2023年第8期2111-2119,共9页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金重点资助项目(U21A20412);首都医科大学优秀青年人才项目(1220090104)。

摘　　要：我国酒精性肝病(alcoholic liver disease,ALD)患者超过6000万,已成为不可忽视的公众健康问题,加之“酒文化”这一社会问题尚难以解决,临床上迫切需要安全有效的ALD防治药物。过去针对ALD的研究主要集中在酒精及其有毒代谢产物的直接损伤作用。但近年来研究显示,ALD的致病原因还包括酒精引起的代谢重编程和内源性代谢物紊乱,这些内源性代谢物虽无直接毒性,但其长期效应不容忽视,特别是可通过表观遗传修饰引起广泛和持久的基因表达谱、信号通路激活异常,把代谢重编程固化为“代谢记忆”,并最终引起病理性改变,进而对ALD的长期进展,特别是肝纤维化/硬化、肝癌的发生产生重要影响。基于此,本文就酒精性肝病发病过程中相关代谢物引起的重要的表观遗传修饰变化及其对酒精性肝病的影响进行综述。并对中药及活性成分在调节表观遗传方面作用进行分析。结果提示,调控表观遗传、改变“代谢记忆”或是中药防治ALD的一种新颖的作用机制。There are more than 60 million alcoholic liver disease(ALD)patients in China,which has become a public health problem that cannot be ignored.Moreover,the social problem of"alcohol culture"is still hardly to solve,so that safe and effective prevention and treatment for ALD are in urgent need clinically.Previous studies on ALD have focused on the direct damaging effects of alcohol and its toxic metabolites,while recent studies have shown that the pathogenesis of ALD also include alcohol metabolic reprogramming and endogenous metabolites disorder.Although the endogenous metabolites have no direct toxicity,its long-term effect should not be ignored.These endogenous metabolites could change epigenetic modifications,cause widespread and persistent abnormal gene expression and signal pathway activation abnormally to promote metabolic reprogramming and stamp it as"metabolic memory",which manifest pathological changes and promote ALD,especially liver fibrosis/cirrhosis and liver cancer.Based on this,the article reviews the important epigenetic modifications caused by related metabolites in ALD and their associated effects.The role of traditional Chinese medicine(TCM)and its active ingredients in regulating epigenetics was also analyzed.The results suggest that regulation of epigenetics and alteration of"metabolic memory"may be a novel mechanism of TCM in the prevention and treatment of ALD.

关 键 词：中药 酒精性肝病 表观遗传修饰 代谢重编程 新药研发 

分 类 号：R966[医药卫生—药理学]