基于网络药理学和分子对接探究桂枝茯苓丸治疗异位妊娠的作用机制  

Mechanism of Guizhi Fuling Pill in Treatment of Ectopic Pregnancy Based on Network Pharmacology and Molecular Docking

作　　者：刘颖[1] 张天婵[1,2] 张梦颖 LIU Ying;ZHANG Tianchan;ZHANG Mengying(Heilongjiang University of Chinese Medicine,Harbin Heilongjiang China 150040;The Second Affiliated Hospital to Heilongjiang University of Chinese Medicine,Harbin Heilongjiang China 150001)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040 [2]黑龙江中医药大学附属第二医院,黑龙江哈尔滨150001

出　　处：《中医学报》2023年第12期2647-2658,共12页Acta Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(81704113)。

摘　　要：目的:应用网络药理学和分子对接探究桂枝茯苓丸治疗异位妊娠的潜在作用机制。方法:在中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选桂枝茯苓丸组方中药有效成分及相应作用靶点。在DrugBank、PharmGkb、GeneCards、TTD和OMIM五大数据库检索异位妊娠相关靶点,并与药物作用靶点进行映射,取交集得到桂枝茯苓丸治疗异位妊娠的潜在靶点。应用Cytoscape_v3.9.1软件构建“桂枝茯苓丸-异位妊娠”调控网络,并使用CytoNCA插件进行拓扑分析筛选关键化合物。将潜在靶点输入STRING在线平台获得蛋白互作(protein-protein interaction,PPI)关系,通过Cytoscape_v3.9.1构建PPI网络并进行拓扑分析筛选核心靶点。使用David数据库对潜在靶点进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析。采用AutoDock vina软件对关键化合物与核心靶点进行分子对接。结果:运用TCMSP数据库筛选得到桂枝茯苓丸有效成分85个,相关靶点525个。于DrugBank、PharmGkb、GeneCards、TTD、OMIM五大数据库检索得到异位妊娠靶点3055个。桂枝茯苓丸有效成分作用靶点与异位妊娠总靶点进行映射得到桂枝茯苓丸治疗异位妊娠的潜在靶点145个。“桂枝茯苓丸-异位妊娠”调控网络分析筛选得到槲皮素、山柰酚、黄芩素等6个关键化合物。PPI网络分析得到10个核心靶点。GO富集分析得到生物学过程725种、分子功能154类和78个细胞组分。KEGG信号通路富集分析得到167条富集通路。分子对接结果表明,关键化合物与核心靶点蛋白间存在良好的亲和力。结论:桂枝茯苓丸中的多种有效成分能够作用于多个潜在靶点并通过多条途径发挥治疗异位妊娠的作用。Objective:To explore the potential mechanism of Guizhi Fuling Pill in treating ectopic pregnancy using network pharmacology and molecular docking.Method:To screen the effective ingredients and corresponding targets of Guizhi Fuling Pill in the traditional Chinese medicine system pharmacology database and analysis platform(TCMSP).Retrieve ectopic pregnancy related targets in the five major databases of DrugBank,PharmaGkb,GeneCards,TTD,and OMIM,and map them with drug action targets to obtain potential targets for the treatment of ectopic pregnancy with Guizhi Fuling Pill.Applying Cytoscape_V3.9.1 software is used to construct the"Guizhi Fuling Pill Ectopic Pregnancy"regulatory network,and the CytoNCA plugin is used for topology analysis to screen key compounds.Input potential targets into the STRING online platform to obtain protein protein interaction(PPI)relationships,using Cytoscape V3.9.1 Build a PPI network and perform topology analysis to screen core targets.Use the David database to perform gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signal pathway enrichment analysis on potential targets.Use AutoDockvina software to perform molecular docking between key compounds and core targets.Result:By using the TCMSP database,85 effective ingredients and 525 related targets were identified from Guizhi Fuling Pills.3055 ectopic pregnancy targets were retrieved from five major databases:DrugBank,PharmaGkb,GeneCards,TTD,and OMIM.Mapping the effective ingredient targets of Guizhi Fuling Pill to the total target of ectopic pregnancy resulted in 145 potential targets for the treatment of ectopic pregnancy with Guizhi Fuling Pill.Six key compounds,including quercetin,kaempferol,and baicalin,were identified through analysis and screening of the regulatory network of"Guizhi Fuling Pill Ectopic Pregnancy".PPI network analysis identified 10 core targets.GO enrichment analysis yielded 725 biological processes,154 molecular functional classes,and 78 cell components.The enrichment

关 键 词：桂枝茯苓丸 异位妊娠 网络药理学 分子对接 作用机制 张仲景 

分 类 号：R285[医药卫生—中药学]