虎杖治疗肺动脉高压作用机制的网络药理学研究

Mechanism of Polygoni Cuspidati Rhizoma et Radix in the Treatment of Pulmonary Arterial Hypertension Based on Network Pharmacology

目的探讨虎杖药材治疗肺动脉高压(PAH)的作用机制。方法通过中药系统药理学数据库和分析平台(TCMSP)和PubMed检索虎杖活性成分,构建活性成分库。通过TCMSP获取活性成分的潜在靶点,利用Uniprot数据库获取潜在靶基因。利用人类基因数据库(GeneCards)和人类孟德尔遗传数据库(OMIM)筛选PAH致病靶点与活性成分靶点基因,构建“药物-活性成分-疾病靶点”可视化网络。将潜在靶点导入String数据库,构建蛋白-蛋白相互作用(PPI)网络;利用DAVID数据库将潜在靶点进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。将节点度值排名前7的活性成分与排名前6的核心靶点利用AutoDockTools和PyMOL软件进行分子对接和可视化分析。结果筛选出活性成分39个,对应靶基因323个,与PAH共同靶点138个。经PPI网络分析,其中关键靶点涉及AKT1,VEGFA,TNF等;GO功能富集分析主要涉及低氧反应、炎性反应、血管再生等功能;KEGG通路富集分析主要涉及细胞增殖、细胞凋亡、炎性反应等信号通路;分子对接结果表明,虎杖药材活性成分白藜芦醇、木犀草素与AKT1,大黄素、芹黄素与TNF均有较好的亲和力。结论虎杖药材可通过多种作用机制预防和治疗PAH。

Objective To investigate the mechanism of Polygoni Cuspidati Rhizoma et Radix in the treatment of pulmonary arterial hypertension(PAH).Methods The active components of Polygoni Cuspidati Rhizoma et Radix were searched through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and PubMed to construct the database of active components.The potential targets of active components were obtained by the TCMSP,and the potential target genes were obtained by the Uniprot database.The pathogenic targets of PAH and target genes of Polygoni Cuspidati Rhizoma et Radix were screened through the GeneCards and Online Mendelian Inheritance in Man(OMIM)databases to construct the"traditional Chinese medicine-active components-disease target"visual network.The potential targets were imported into the String database to construct the protein-protein interaction(PPI)network.Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted on the potential targets through the DAVID database.Molecular docking and visual analysis were conducted on the active components ranking the top sever in the Degree value and the key targets ranking the top six through AutoDock tools and PyMOL software.Results Thirty-nine active components were screened from Polygoni Cuspidati Rhizoma et Radix,including 323 corresponding target genes and 138 common targets corresponded with PAH.PPI network analysis showed that the key targets involved AKT1,VEGFA,TNF and so on.Go function enrichment analysis mainly involved hypoxic response,inflammatory response,vascular regeneration and other functions.KEGG pathway enrichment analysis mainly involved signaling pathways such as cell proliferation,apoptosis and inflammatory response.Molecular docking results showed that resveratrol and luteolin had a good affinity with AKT1,emodin and apigenin had a good affinity with TNF.Conclusion Polygoni Cuspidati Rhizoma et Radix can prevent and treat PAH through a variety of mechanisms.