解毒化瘀颗粒对肝衰竭的疗效与作用机制研究

Study on the Therapeutic Effect and Mechanism of Jiedu Huayu Granules (解毒化瘀颗粒) on Liver Failure

目的:运用Meta分析、GEO基因芯片挖掘、生物信息学及分子对接技术,分析解毒化瘀颗粒治疗ACLF的疗效与机制。方法:检索PubMed、Web of Science、Cochrane、Embase、SinoMed、CNKI、VIP、WanFang数据库,根据纳入与排除标准筛选文献,运用R软件对观察指标进行Meta分析。通过GEO、TCMSP、SymMap、PharmMapper等数据库,取得解毒化瘀颗粒的化学成分,预测药物靶点,收集ACLF相关靶点,运用R软件、PyMOL、AutoDockTools1、AutoDock Vina等软件进行GO富集分析、KEGG富集分析、WGCNA共聚类分析和分子对接验证。结果:通过Meta分析发现,在总有效率、死亡率、MELD评分、血清总胆红素、血清白蛋白、血清丙氨酸氨基转移酶、凝血酶原活动度指标方面,治疗组均优于对照组(P<0.05)。生物信息学分析发现,解毒化瘀颗粒干预ACLF的靶点有52个;主要化学成分有8-异戊烯基山奈酚、异鼠李素、异泽兰黄素等;核心靶点有CYP3A4、CYP1A2、CYP1A1、NQO1、ABCG2等;富集分析涉及类固醇代谢、激素代谢、细胞基质连接、黏着斑、铁离子结合、四吡咯结合、化学致癌作用-受体激活、亚油酸代谢、类固醇激素生物合成、细胞色素P450代谢通路、花生四烯酸代谢、胆汁分泌等;56组分子对接得分均<-5.0 kcal/mol。结论:在西医治疗的基础上加用解毒化瘀颗粒,能够改善ACLF的预后,且具有多途径、多成分的作用机制。

Objective:To analyze the efficacy and mechanism of Jiedu Huayu Granules in the treatment of acute-on-chronic liver failure(ACLF)by using Meta analysis,GEO gene chip mining,bioinformatics and molecular docking technology.Methods:PubMed,Web of Science,Cochrane,Embase,SinoMed,CNKI,VIP,WanFang databases were searched,literatures were screened according to the inclusion and exclusion criteria,and R software was used to perform Meta-analysis on the observed indicators.Through GEO,TCMSP,SymMap,PharmMapper and other databases,the chemical composition of Jiedu Huayu Granules was obtained,and drug targets were predicted.ACLF-related targets were collected,and R software,PyMOL,AutoDockTools1,AutoDock Vina and other software were used for GO enrichment analysis,KEGG enrichment analysis,WGCNA co-clustering analysis and molecular docking verification.Results:Through Meta-analysis,it was found that the treatment group was superior to the control group in terms of total effective rate,mortality,MELD score,serum total bilirubin,serum albumin,serum alanine aminotransferase and prothrombin activity index(P<0.05).Bioinformatics analysis showed that there were 52 targets for Jiedu Huayu Granules to intervene in ACLF.The main chemical constituents are 8-prenyl-kaempferol,isorhamnetin,eupatilin,etc.The core targets were CYP3A4,CYP1A2,CYP1A1,NQO1,ABCG2,etc.Enrichment analysis involved steroid metabolic process,hormone metabolic process,cell substrate junction,focal adhesion,iron ion binding,tetrapyrrole binding,chemical carcinogenesis-receptor activation,linoleic acid metabolism,steroid hormone biosynthesis,cytochrome P450 metabolic pathway,arachidonic acid metabolism,bile secretion,etc.The molecular docking scores of 56 groups were<-5.0 kcal/mol.Conclusion:Jiedu Huayu Granules can improve the prognosis of ACLF on the basis of Western medical treatment,and has a multi-channel and multi-component mechanism of action.