基于网络药理学的六味地黄丸治疗冠心病的分子机制研究

Molecular Mechanism of Liuwei Dihuang Pills in Treating CoronaryHeart Disease Based on Network Pharmacology

目的运用网络药理学分析六味地黄丸治疗冠心病的分子机制。方法从中药系统药理学分析平台(TCMSP)获得与六味地黄丸中6味中药相关的所有化学成分和作用靶点,运用Cytoscape 3.2.1软件构建化合物靶点相互作用网络图,利用TTD、Drugbank、DisGeNET数据库筛选冠心病相关的疾病靶点,将冠心病靶点与药物靶点进行Venn分析,筛选出二者的共同靶点,应用STRING平台构建蛋白-蛋白相互作用(PPI)网络模型。通过DAVID(Version 6.8)数据库对疾病与药物共同靶点进行Gene Ontology(GO)富集分析、KEGG通路富集分析。结果共筛选出六味地黄丸的43种主要成分及与治疗冠心病相关的关键靶点85个,靶点主要涉及调节脂多糖代谢、炎症反应、细胞分裂、细胞因子活性、DNA复制及其转录等生物过程,通过参与TNF、HIF-1、PI3K/Akt、Estrogen、TLRs、NF-κB、cGMP-PKG、cAMP等信号通路治疗冠心病。结论本研究从多角度探索了六味地黄丸治疗冠心病可能的作用机制,揭示了六味地黄丸具有多成分、多靶点和多途径治疗疾病的特点,为其临床应用及进一步研究其药效作用机制奠定基础。

Objective Using network pharmacology to analyze the molecular mechanism of Liuwei Dihuang Pills in treating coronary heart disease.Methods Obtained all chemical constituents and targets related to 6 traditional Chinese medicines in Liuwei Dihuang Pills from the Traditional Chinese Medicine Systems Pharmacology Analysis Platform(TCMSP).Cytoscape 3.2.1 software was used to construct a network map of compound target interactions.TTD,Drugbank,and DisGeNET databases were used to screen coronary heart disease-related disease targets.Venn analysis of coronary heart disease targets and drug targets were performed to screen out the common targets.Protein-protein interaction(PPI)network model was constructed by STRING platform.Gene Ontology(GO)enrichment analysis and KEGG pathway enrichment analysis of common targets of diseases and drugs were conducted by DAVID(Version 6.8)database.Results A total of 43 major components of Liuwei Dihuang Pills and 85 key targets related to the treatment of coronary heart disease were screened.The targets are mainly related to the regulation of lipopolysaccharide metabolism,inflammatory reaction,cell division,cytokine activity,DNA replication and transcription.Treatment coronary heart disease by participating in TNF,HIF-1,PI3K/Akt,Estrogen,TLRs,NF-κB,cGMP-PKG,cAMP and other signaling pathways.Conclusion This study explored the possible mechanism of Liuwei Dihuang Pills in the treatment of coronary heart disease from various perspectives,and revealed that Liuwei Dihuang Pills has the characteristics of multi-component,multi-target and multi-channel treatment of diseases,laying a foundation for its clinical application and further study of its pharmacodynamic mechanism.