巨噬细胞极化在肝纤维化中的作用和调控机制以及中国传统医药的干预  

The role and regulation mechanism of macrophage polarization in liver fibrosis and the intervention of traditional Chinese medicine

作　　者：彭望霞 陆华冠 谢新 刘建军 PENG Wang-xia;LU Hua-guan;XIE Xin;LIU Jian-jun(Science and Technology Innovation Centre/State Key Laboratory Cultivation Base of Chinese Medicine Powder and Innovative Drugs,Hunan University of Traditional Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学科技创新中心/中药粉体与创新药物省部共建国家重点实验室培育基地,长沙410208

出　　处：《中国新药杂志》2024年第10期1021-1031,共11页Chinese Journal of New Drugs

基　　金：湖南省教育厅重点项目(18A228);湖南中医药大学校级研究生创新课题项目(2022CX95)。

摘　　要：肝巨噬细胞是肝脏中重要的免疫细胞,具有显著的异质性和可塑性。在肝脏慢性损伤条件下,驻留的肝巨噬细胞和被招募到损伤部位的外周单核细胞在肝微环境中各种因素的刺激下,被激活并极化为多种巨噬细胞表型,发挥不同的功能。近年来的研究表明,肝巨噬细胞极化对肝纤维化进程起关键的调节作用,但机制尚不完全清楚。本文综述了Notch、转化生长因子-β(transforming growth factor-β,TGF-β)/Smads、Janus激酶/信号传导及转录激活因子(JAK/STAT)和Toll样受体4(TLR4)/核转录因子κB(NF-κB)等信号通路调节巨噬细胞极化参与肝纤维化进程的分子机制。此外,中国传统医药具有多成分、多靶点的优势,对慢性肝病和肝纤维化具有良好的疗效,本文也综述了近年来中药方剂和单体化合物靶向肝巨噬细胞的抗纤维化作用机制,并为临床应用提出新的见解。Hepatic macrophages are important immune cells in the liver and exhibit remarkable heterogeneity and plasticity.Under conditions of chronic liver injury,resident hepatic macrophages and peripheral monocytes are recruited to the site of injury,activated by various factors in the liver microenvironment,and polarized into different functional macrophage phenotypes.Recent studies have shown that liver macrophage polarization plays a key regulatory role in the progression of liver fibrosis,but the mechanism is not fully understood.In this review,we review the molecular mechanisms of Notch,transforming growth factor-β(TGF-β)/Smads,Janus kinase/signal transducer and activator of transcription(JAK/STAT),and Toll-like receptor 4(TLR4)/nuclear transcription factor kB(NF-KB)pathways regulating macrophage polarization and involvement in liver fibrosis.Moreover,traditional Chinese medicine has positive therapeutic effects on chronic liver disease and hepatic fibrosis due to its multi-component and multi-target advantages.This paper also reviewed the mechanisms of antifibrotic effects of herbal and monomeric compounds targeting hepatic macrophage polarization in recent years,providing new insights for clinical application.

关 键 词：肝纤维化 巨噬细胞极化 中药复方 单体化合物 

分 类 号：R967[医药卫生—药理学]