基于网络药理学及分子对接探讨冠心2号方治疗冠心病的作用机制  

The Mechanism of Guanxin 2 Prescription in the Treatment of Coronary Heart Disease Based on Network Pharmacology and Molecular Docking

作　　者：刘振飞 刘爽[1] 张世亮[2] LIU Zhenfei;LIU Shuang;ZHANG Shiliang(Shandong University of Traditional Chinese Medicine,Jinan 250013,Shandong,China)

机构地区：[1]山东中医药大学,济南250013 [2]山东中医药大学附属医院,济南250013

出　　处：《中西医结合心脑血管病杂志》2022年第11期1929-1939,共11页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

摘　　要：目的利用网络药理学及分子对接的方法探讨冠心2号方治疗冠心病(CHD)的作用机制。方法运用中药系统药理学数据库与分析平台(TCMSP)对冠心2号方中的药物主要有效成分和靶点进行筛选,利用Cytoscape 3.7.2软件构建药物-成分-靶点-疾病网络图;基于STRING数据库建立冠心2号方治疗CHD的蛋白质-蛋白质相互作用(PPI)网络图,并进行拓扑分析,筛选得出冠心2号方治疗冠心病的核心靶点。使用DAVID数据库对药物-疾病交集靶点进行生物通路及富集分析。结果冠心2号方药物-成分-靶点-疾病网络图包含124个有效成分,度值最高的前5位分别为槲皮素、山奈酚、木犀草素、黄芩素、β-谷甾醇。相对应靶点74个,核心靶点(Degree≥38)17个。自由度较高的靶点有白细胞介素6(IL6)、血管内皮生长因子A(VEGFA)、肿瘤坏死因子(TNF)、细胞肿瘤抗原p53(TP53)、丝裂原活化蛋白激酶1(MAPK1)。基因本体(GO)条目93条,主要为一氧化氮生物合成过程的正调控、平滑肌细胞增殖的正调控等。京都基因和基因组百科全书(KEGG)富集通路74条,涉及的通路主要有NOD样受体信号通路、TNF信号通路等。分子对接结果显示所含活性化合物与CHD相关靶点的结合能均<-20.9 kJ/mol,结合活性较好。结论冠心2号方在治疗冠心病时具有多通路、多靶点、多成分的特点。本研究探讨了冠心2号方的主要活性成分、相关靶点及通路,为后续处方的优化及临床治疗CHD的疗效评价指标提供参考。Objective To explore the mechanism of Guanxin 2 Prescription in the treatment of coronary heart disease(CHD)by network pharmacology and molecular docking.Methods The main effective components and targets in Guanxin 2 Prescription were screened by traditional Chinese medicine(TCM)pharmacology database and analysis platform database(TCMSP),and the network diagram of TCM-component-target-disease was constructed by Cytoscape 3.7.2 software.The protein-protein interaction(PPI)network diagram of Guanxin 2 Prescription for CHD treatment was established based on STRING database,and topology analysis was conducted to screen the core targets of Guanxin 2 Prescription for CHD treatment.Biological pathways and enrichment analysis of drug-disease intersection targets were performed using DAVID database.Results The TCM-component-target-disease network diagram of Guanxin 2 Prescription contained 124 active components,and the top 5 with the highest degree value were quercetin,kaempferol,luteolin,baicalein andβ-sitosterol.There were 74 corresponding targets and 17 core targets(Degree≥38).The targets with high degree of freedom were interleukin 6(IL6),vascular endothelial growth factor A(VEGFA),tumor necrosis factor(TNF),the cell tumor antigen p53(TP53),and mitogen-activated protein kinase 1(MAPK1).There were 93 Gene Ontology(GO)items,including positive regulation of nitric oxide biosynthesis and smooth muscle cell proliferation.There were 74 Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways,involving NOD like receptor signaling pathway,TNF signaling pathway,etc.The molecular docking results showed that the binding energies of the active compounds with CHD-related targets were all<-20.9 kJ/mol,indicating better binding activity.Conclusion Guanxin 2 Prescription with the characteristics of multiple pathways,multiple targets and multiple components can be used to treat coronary heart disease.This paper,will provid reference for the development optimization of subsequent prescriptions and the efficacy evaluation indexes of cli

关 键 词：冠心病 冠心2号方 网络药理学 分子对接 作用机制 

分 类 号：R54[医药卫生—心血管疾病]