通过网络药理学和动物实验探讨苦黄颗粒治疗非酒精性脂肪性肝病的作用机制  

Mechanism of Kuhuang Granules in treating non-alcoholic fatty liver disease based on network pharmacology and experimental validation

作　　者：杨金凤 薛静波 陶艳艳[1] 黄恺 吕靖[1] 刘成海[1,2,3] YANG Jin-feng;XUE Jing-bo;TAO Yan-yan;LIU Cheng-hai(The second department of Liver Disease,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,(Shanghai,201203),China;Shanghai Key Laboratory of Traditional Chinese Clinical Medicine,(Shanghai,201203),China;Key Laboratory of Liver and Kidney Diseases(Shanghai University of Traditional Chinese Medicine),(Shanghai,201203),China)

机构地区：[1]上海中医药大学附属曙光医院肝二科,上海201203 [2]上海市中医临床重点实验室 [3]肝肾疾病病证教育部重点实验室(上海中医药大学)

出　　处：《中西医结合肝病杂志》2022年第1期58-62,共5页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：上海市临床重点专科建设项目(No.shslczdzk01201)。

摘　　要：目的:基于网络药理学和动物实验验证,研究苦黄颗粒治疗非酒精性脂肪性肝病(NAFLD)的作用机制。方法:利用中药系统药理学分析平台(TCMSP)查找苦黄颗粒中5味中药的化学成分并进行活性化合物筛选。利用Pubchem、Swiss Target Prediction、SEA和STITCH数据获取苦黄颗粒活性化合物的作用靶点。利用DisGeNET和GeneCards数据库查找NAFLD的疾病靶点,取交集后得到苦黄颗粒治疗NAFLD的潜在靶点。使用String数据库构建蛋白质—蛋白质互作网络,并在Metascape平台进行PPI网络靶点模块分析。利用DAVID平台进行靶点GO分析和KEGG通路富集分析。使用Cytoscape软件进行化合物—靶点网络拓扑分析,并构建“药材—化合物—靶点—通路”网络。采用高脂饲料复合CCl_(4)制造脂肪肝小鼠模型进行网络药理学部分结果的体内实验验证。结果:经筛选后得到苦黄颗粒治疗NAFLD的核心化合物10个(甘草酚、菜豆蛋白、青蒿素A、儿茶素等),核心靶点14个(CCND1、EGFR、IL1B、MMP2/9、PPARG等)。通路富集分析获得相关通路96条,TNF、Toll样受体等信号通路可能为关键通路。苦黄颗粒可显著抑制脂肪肝小鼠肝组织炎症及TNF-α、TLR4、Myd88的表达。结论:初步挖掘苦黄颗粒治疗NAFLD的核心化合物和作用靶点,苦黄可能通过抑制脂肪肝小鼠TNF-α、TLR4、Myd88表达起到抗炎作用,为深入研究作用机制提供参考依据。Objective:To explore the mechanism of Kuhuang Granules(KH)in treating non-alcoholic fatty liver disease(NAFLD)by means of network pharmacology and experimental verification.Methods:We found the core target and key signal pathway of KH in the treatment of nonalcoholic fatty liver disease based on the network pharmacological method.The results of network pharmacology were partly verified in vivo by the CCl4 fatty liver mouse model.Results:Ten key compounds(Glycyrol,Phaseolin,artemisinin A,catechin,etc.)and 14 key targets(CCND1,EGFR,IL1B,MMP2/9,PPARG,etc.)of KH in treating NAFLD were obtained by screening.According to KEGG enrichment analysis,96 pathways were identified,among which the TNF signaling pathway and Toll signaling pathway may be the main signaling pathway in which these pathways play a role.Kuhuang granule can significantly downregulate liver inflammation and the RNA expression of TNF α,TLR4,and MyD88 in the high-fat diet combined with CCl_(4) induced fatty liver.Conclusion:The study explores the key compounds and targets of KH in treating NAFLD,Kuhuang may play an anti-inflammatory role by inhibiting the expression of TNFα,TLR4,and MyD88 in the fatty liver mice,and provides references to develop a further mechanism.

关 键 词：非酒精性脂肪性肝病 苦黄颗粒 网络药理学 实验验证 

分 类 号：R575.5[医药卫生—消化系统]