吉林大学学报(医学版) ›› 2024, Vol. 50 ›› Issue (5): 1450-1456.doi: 10.13481/j.1671-587X.20240532

• 综述 • 上一篇    

肝纤维化发病的分子机制及其相关治疗靶点的研究进展

廖昭辉,谢正元()   

  1. 南昌大学第二附属医院消化内科,江西 南昌 330006
  • 收稿日期:2023-04-07 出版日期:2024-09-28 发布日期:2024-10-28
  • 通讯作者: 谢正元 E-mail:xzyxzy1230@163.com
  • 作者简介:廖昭辉(1994-),男,江西省南昌市人,在读硕士研究生,主要从事消化系统肝脏疾病方面的研究。
  • 基金资助:
    国家自然科学基金项目(82260131);江西省科技厅自然科学基金重点项目(20212ACB206017);江西省科技厅科技重点研发项目(20203BBG73044);江西省教育厅科学技术研究项目(GJJ200193)

Research progress in molecular mechanism of hepatic fibrosis and related therapeutic targets

Zhaohui LIAO,Zhengyuan XIE()   

  1. Department of Gastroenterology,Second Affiliated Hospital,Nanchang University,Nanchang 330006,China
  • Received:2023-04-07 Online:2024-09-28 Published:2024-10-28
  • Contact: Zhengyuan XIE E-mail:xzyxzy1230@163.com

摘要:

肝纤维化(HF)是一种临床上较为常见的肝脏受损后的病理性修复反应,是慢性肝病转向肝硬化的核心环节。HF发病的分子机制复杂,肝脏受损引起多种细胞释放一系列细胞因子,进而启动下游通路进行信号转导,活化肝星状细胞(HSCs)并使其向肌成纤维细胞(MFBs)转化。MFBs可释放大量细胞外基质(ECM),进而破坏肝脏正常结构,导致HF的发生发展。HF相关治疗靶点仍处于动物实验阶段,尚未应用于临床。现对HF发病机制中HSCs和ECM所涉及的信号通路及相应因子,如转化生长因子β(TGF-β)/Smad相关信号通路、血小板衍生生长因子(PDGF)、基质金属蛋白酶(MMPs)、金属蛋白酶组织抑制因子(TIMPs)和结缔组织生长因子(CTGF)等进行综述,分析相关的治疗靶点,为治疗HF的新药研发提供理论依据。

关键词: 肝纤维化, 肝星状细胞, 细胞外基质, 分子机制, 治疗靶点

Abstract:

Hepatic fibrosis (HF) is a common pathological repair response occurring after liver injury and is a critical stage in the progression of chronic liver diseases towards cirrhosis. The molecular mechanisms of HF occurrence are complex. Liver injury triggers the release of various cytokines by multiple cell types, and initiates the downstream signaling pathways to activate the hepatic stellate cells (HSCs) and transform them into myofibroblasts (MFBs). MFBs can release large quantities of extracellular matrix (ECM), thereby disrupt the normal liver architecture and lead to the occurrence and development of HF. The potential therapeutic targets for HF are still in the experimental animal phase, and there are no clinical applications yet. This review summarizes the signaling pathways and related factors involving HSCs and ECM in HF, such as the transforming growth factor-β (TGF-β)/Smad signaling pathway, platelet-derived growth factor (PDGF), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and connective tissue growth factor (CTGF). It also discusses the related therapeutic targets, and provids the theoretical basis for the development of new drugs for HF.

Key words: Hepatic fibrosis, Hepatic stellate cell, Extracellular matrix, Molecular mechanism, Therapeutic target

中图分类号: 

  • R575.2