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中药调控Toll样受体4/核因子-κB通路改善非酒精性脂肪性肝炎的研究进展

田格格 夏恩蕊 张素妍 张顺贞 徐福荣

引用本文:
Citation:

中药调控Toll样受体4/核因子-κB通路改善非酒精性脂肪性肝炎的研究进展

DOI: 10.3969/j.issn.1001-5256.2021.12.047
基金项目: 

国家自然科学基金 (81760818)

云南省高校中医证候微观辨证重点实验室 (20190720)

云南省科技厅中医联合专项 (2018FF001(-042))

详细信息
    通信作者:

    张顺贞,694415176@qq.com

    徐福荣,xfrong99@163.com

  • 中图分类号: R575.5

Research advances in traditional Chinese medicine in improving nonalcoholic steatohepatitis by regulating the Toll-like receptor 4/nuclear factor-kappa B signaling pathway

Research funding: 

National Natural Science Foundation of China (81760818);

Key Laboratory of Microcosmic Syndrome Differentiation of TCM Syndrome in Yunnan Province (20190720);

Joint Special Project of Traditional Chinese Medicine of Yunnan Provincial Science and Technology Department (2018FF001(-042))

  • 摘要: 非酒精性脂肪性肝炎(NASH)是非酒精性脂肪性肝病的严重类型,可发展为威胁生命的肝硬化和肝癌。Toll样受体4(TLR4)是先天免疫中的一类模式识别受体,被激活可引发级联反应,活化介导炎症反应的核因子-κB(NF-κB)。TLR4/NF-κB通路是经典的炎症通路。临床上用中药治疗NASH取得了良好的疗效,TLR4/NF-κB通路是中药治疗NASH的途径之一,通过检索相关文献,总结了可调控TLR4/NF-κB通路改善NASH的中药活性成分和复方,旨在为今后的研究和用药提供思路。

     

  • 图  1  TLR4/NF-κB通路

    注:TRAF-6,肿瘤坏死因子相关因子。当肝脏中各类免疫细胞与非免疫细胞表面的TLR4被激活,MyD88适配子磷酸化,活化TRAF-6使得TAK1、IKKs被激活[13]。IκB在IKKs的作用下从静息状态下的NF-κB聚合体中分离,与IκB分离后的NF-κB进入细胞核,介导IL-6、IL-1β、TNFα等炎症因子的基因转录和释放[14]

    表  1  中药活性成分调控TLR4/NF-κB通路改善NASH

    类别 药物 造模方式 通路相关分子表达情况 相关炎症因子表达情况 文献
    黄酮类 杨梅素 低蛋氨酸和胆碱缺乏及L-氨基酸限定的高脂饮食/LPS干预 下调TLR4、MyD88、p-NF-κB/NF-κB、p-IκBα/IκBα 下调TNFα、IL-6、IL-1β;上调IL-10 [15]
    槲皮素 蛋氨酸-胆碱缺乏饮食 下调TLR4、NF-κB P65 下调TNF-α、IL-6 [16]
    黄芩苷 蛋氨酸-胆碱缺乏饮食 下调TLR4、MyD88、p-NF-κB p65 下调TNF-α、IL-6、IL-1β [17]
    胡桃苷 高果糖饮食 下调TLR4、MyD88、IRAK4、IRAK1、TRAF6、TAK1、P-IKKα、P-IκBα、p-NF-κB 下调TNFα、IL-1β、IL-18、IL-6 [18]
    银杏黄酮 高脂饮食 下调TLR4、p-NF-κB p65 下调IL-6、TNFα [19]
    豹皮樟总黄酮 脂肪乳剂 下调TLR4、NF-κB 下调TNFα [20]
    萜类 白果内酯 高脂饮食 下调TLR4、TAK1、p-NF-κB p65/NF-κB p65 下调TNFα、IL-6、IL-1β [21]
    青蒿琥酯 高脂饮食 下调TLR4、MyD88、NF-κB 下调TNFα [22-23]
    黄芪甲苷 高脂饮食 下调TLR4、MyD88、NF-κB p65 下调IL-6、TNFα、IL-8 [24]
    绞股蓝总苷 高脂饮食/游离脂肪酸干预 下调TLR4、MyD88、p-NF-κB/NF-κB、p-IκBα/IκBα 下调IL-1β、TNFα [25]
    醌类 紫草素 蛋氨酸-胆碱缺乏饮食 下调P-P65 下调TNFα、IL-6、IL-1β [26]
    决明子蒽醌苷 高脂饮食 下调TLR4、NF-κB 下调IL-1β、IL-6、TNFα、IL-1α [27]
    大黄酸 高脂高果糖饮食 下调TLR4、MyD88、NF-κB [28]
    生物碱类 小檗碱 高脂饮食 下调TLR4、MyD88、NF-κB p65 下调IL-6、TNFα、IL-1β [29]
    槐果碱 油酸干预 下调TLR4、P-IKKα/β、IKKα、IKKβ 下调IL-6、TNFα [31]
    多酚类 姜黄素 高脂饮食 TLR4、MyD88、NF-κB p65 IL-6、TNFα、IL-1β [32]
    二苯乙烯苷 高脂饮食 TLR4、P-IKKα/β、IKKα、IKKβ IL-6、TNFα [33]
    多糖类 枸杞多糖 高脂饮食 下调P-P65 下调TNFα、IL-6、IL-1β [34]
    狗肝菜多糖 高脂饮食 下调TLR4、p-NF-κB p65 下调IL-6、TNFα、IL-1β [19]
    其他类 滨蒿内酯 蛋氨酸-胆碱缺乏饮食 TLR4、MyD88、IκBα、p-NF-κB p65 IL-1β、TNFα、IL-6、IL-10 [35]
    砂仁挥发油 高脂饮食 TLR4、NF-κB、Ikk、IκB TNFα、IL-6、IL-1α、IL-10 [36]
    丹参提取物 高脂饮食 TLR4、TIRAP、IRAK1、IRAK4、TRAF6、P-IκB、IκB、NF-κB P65、P-NF-κB P65 TNFα、IL-1β、IL-6 [37]
    下载: 导出CSV

    表  2  中药复方调控TLR4/NF-κB通路改善NASH

    中药复方 功效 造模方式 通路相关分子表达情况 相关炎症因子表达情况 文献
    祛痰活血方 疏肝健脾、活血化瘀 蛋氨酸-胆碱缺乏饮食 下调TLR4、MyD88、NF-κB [42]
    附子理中汤 温阳健脾 脂肪乳灌胃 下调CD4、TLR4、NF-κB p65 下调IL-2、IL-6、TNFα [43]
    加味泽泻汤 健脾利湿 高脂饮食 下调TLR4、MyD88、NF-κB p65、p-p65 [44]
    健脾清化饮 健脾益气、清热化湿 高脂饮食 下调TLR4、MyD88、NF-κB 下调TNFα [45]
    复方渣金颗粒 健脾化湿、活血化瘀、疏肝解郁 高脂高果糖饮食 下调TLR4、MyD88 下调TNFα [46-47]
    大柴胡汤 疏肝利胆健脾 高脂高果糖饮食 下调TLR4、NF-κB 下调TNFα [48]
    下载: 导出CSV
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  • 收稿日期:  2021-05-22
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