基于网络药理学和分子对接分析三七-红花药对抗心肌缺血再灌注损伤的作用机制

Mechanism of Panax Notoginseng-Carthamus Tinctorius against Myocardial Ischemia Reperfusion Injury by Network Pharmacology and Molecular Docking

目的利用网络药理学方法及分子对接技术探讨三七-红花药对抗心肌缺血再灌注损伤的作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP)数据库筛选出三七和红花所含有效化学成分及相应的靶蛋白,在Uniprot数据库将预测出的靶蛋白名转换为基因名;通过GeneGards和OMIM数据库筛选出心肌缺血再灌注损伤的靶点基因;利用Venn在线软件获取药物与疾病的共同靶点基因,并以Venn图的形式展现,运用Cytoscape软件构建“化合物-靶点”可视化网络图;运用String数据库结合Cytoscape软件绘制蛋白相互作用(PPI)网络,并进行网络拓扑学分析;使用分子对接软件(AutoDock Vina)对三七和红花中9个关键药效成分与度值排名前10位的核心靶点进行分子对接验证;利用Bioconductor R软件包对靶点基因进行基因本体(GO)功能和京都基因和基因组百科全书(KEGG)通路富集分析。结果经筛选后得到三七-红花药对27个有效化学成分,203个靶点基因、疾病相关靶点基因511个;通过Venn图获得81个药物疾病共同靶点基因;核心靶点涉及趋化因子CC基元配体(CCL2)、白细胞介素6(IL-6)、丝氨酸/苏氨酸激酶1(AKT1)、基质金属肽酶9(MMP9)等。GO功能分析得出1284个生物学过程、32个细胞组成、67个分子功能,KEGG通路分析发现125条相关信号通路。结论本研究预测“三七-红花”药对可通过CCL2、IL-6、AKT1、MMP9等多靶点及IL-17信号通路、磷脂酰肌醇3激酶(PI3K)-Akt信号通路等多通路来治疗心肌缺血再灌注损伤的可能作用机制,为进一步深入探讨该药对抗心肌缺血再灌注损伤作用的物质基础和分子生物学试验奠定了基础。

Objective To investigate the mechanism of panax notoginseng-carthamus tinctorius against myocardial ischemia-reperfusion injury by network pharmacological method and molecular docking technology.Methods The effective components and corresponding target proteins of panax notoginseng and carthamus tinctorius were screened by TCMSP,and the predicted target protein names were converted to gene names in Uniprot database.The target of myocardial ischemia reperfusion injury was screened through the Genecards and OMIM database.Venn online software was used to obtain the common target of drugs and diseases,and to show them in the form of Venn map,then the visual analysis and the"compound-target"network diagram were constructed by Cytoscape software.String database and Cytoscape software were used to draw the Protein-Protein interaction(PPI)network and carry out the network topology analysis.AutoDock Vina was used to verify the molecular docking of 9 key pharmacodynamic components and top 10 core targets in panax notoginseng-carthamus tinctorius.The Bioconductor R package was used to perform gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis on effective targets.Results After screening,27 effective components and 203 potential target genes of panax notoginseng-carthamus tinctorius and 511 disease-related target genes were obtained.Eighty-one common target genes between drugs and diseases were obtained through Venn diagrams,and the core target involved CCL2,IL-6,AKT1,MMP9 and so on.Go function analysis showed 1284 biological processes,32 cell components,67 molecular functions,and KEGG pathway analysis found 125 related signal pathways.Conclusion Panax notoginseng-carthamus tinctorius could treat myocardial ischemia-reperfusion injury through multiple targets such as CCL2,IL-6,AKT1,MMP9,and multiple pathways such as IL-17 signaling pathway and PI3K-Akt signaling pathway,which laid a foundation for further study on the material basis and molecular biological test of the compound.