中医药调控程序性细胞死亡干预肝纤维化的研究进展
DOI: 10.12449/JCH240127
Research advances in traditional Chinese medicine regulation of programmed cell death in intervening against hepatic fibrosis
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摘要: 肝纤维化(HF)是一种由于慢性肝损伤导致的肝组织结构异常修复的病理过程,其发病机制尚未完全阐明。相关研究表明,程序性细胞死亡可能与HF的发生有关,而中医药在调控程序性细胞死亡干预HF方面有着显著疗效。本文概述了程序性细胞死亡影响HF的主要机制,并从中医角度出发探讨中医药调控程序性细胞死亡改善HF的可能机制,为中医药防治肝纤维化提供新思路。Abstract: Hepatic fibrosis (HF) is a pathological process of abnormal repair of liver tissue structure caused by chronic liver injury, and its pathogenesis has not been fully clarified. Related studies have shown that programmed cell death may be associated with the onset of HF, and traditional Chinese medicine (TCM) has a significant effect in regulating programmed cell death to intervene against HF. This article reviews the main mechanism of the influence of programmed cell death on HF and discusses the possible mechanism of TCM regulation of programmed cell death in improving HF, which provides new ideas for TCM prevention and treatment of HF.
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Key words:
- Hepatic Fibrosis /
- Traditional Chinese Drugs /
- Programmed Cell Death
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表 1 近5年通过调控PCD抗肝纤维化的其他中药复方和中药活性成分总结
Table 1. Summary of other traditional Chinese medicine formulas and active ingredients for regulating PCD in the past five years to combat hepatic fibrosis
类型 中药复方/中药有效成分 药物组成/有效成分来源 实验模型 作用机制及药理效应 细胞凋亡 木脂素[51] 中药五味子主要提取物 CCl4诱导的HF小鼠模型 下调α-SMA/ETBR/PLCβ/CHOP/Bax、Caspase12/9/3凋亡因子表达,达到抗细胞凋亡和保肝作用 桔梗皂苷D[52] 中药桔梗干燥根的提取物 体外HSC细胞模型 增加Bax、细胞色素C、cle-Caspase9/3凋亡蛋白的表达水平,减缓肝纤维化和HSC的活化 杨桃根提取物[53] 杨桃根 CCl4诱导的HF大鼠模型 抑制α-SMA,TIMP2,TGF-β1,Smad2、3和4,BAX和Caspase3蛋白的表达,同时显著提高Smad7的mRNA表达以及Smad7和Bcl-2的蛋白表达,达到抗纤维化作用 冬虫夏草菌丝体多糖、绞股蓝总皂苷和苦杏仁苷[54] 扶正化瘀胶囊主要成分 CCl4诱导的HF大鼠模型 降低ALT、AST水平,下调α-SMA、TGF-β1、Col-Ⅰ、Fas、TNF-R1、Caspase3/8/9/10、线粒体Bax、Bak和细胞色素C的蛋白表达 黄芩素[55] 黄芩的主要活性成分 CCl4诱导的HF小鼠模型 增强HSC-T6细胞中cle-Caspase9/3表达和Bax/Bcl-2比例。通过调节HSC的活化和凋亡来减轻HF 自噬 丹酚酸b[56] 丹参的根提取物 CCl4诱导的HF小鼠模型 抑制HSC激活的生物标志物(α-SMA和Ⅰ型胶原)表达,抑制HSC的活化和胶原沉积以减轻肝纤维化的发生 益气柔肝汤[57] 太子参、生地、枸杞子、首乌、白术、白芍、茵陈、虎杖、苡仁、黄芪等 CCl4诱导的HF大鼠模型 下调MAPK和PI3K/Akt信号通路,上调PPAR和AMP活化蛋白激酶,改善肝功能、降低HSC活性和减少ECM沉积,以达到抗肝纤维化效果 焦亡 合欢皮-白蒺藜药对[58] 中草药合欢皮、白蒺藜药对 体外细胞实验 下调NLRP3、caspase-1、α-SMA及GSDMD蛋白和基因表达,抑制细胞焦亡的经典通路,该机制可能参与其抗肝纤维化作用 铁死亡 紫花前胡素[59] 白花前胡和紫花前胡根的提取物 CCl4诱导的HF小鼠模型 通过调节Gpx4和GSH水平下降,Fe2+、ROS和Ptgs2水平增加,以促进体外活化造血干细胞的铁死亡,达到HF作用 -
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