基于网络药理学和分子对接探讨二至丸治疗更年期高血压的作用机制  

Exploring the Mechanism of Erzhi Pill in the Treatment of Menopausal Hypertension Based on Network Pharmacology and Molecular Docking

作　　者：孟园 李平 刘欣[1,2] 袁晶 MENG Yuan;LI Ping;LIU Xin;YUAN Jing(Third Affiliated Hospital of Beijing University of Chinese Medicine,Beijing 100029;Beijing University of Chinese Medicine,Beijing 100029)

机构地区：[1]北京中医药大学第三附属医院,北京100029 [2]北京中医药大学,北京100029

出　　处：《世界中西医结合杂志》2021年第6期1044-1048,1057,共6页World Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金项目(81803905);2019年北京中医药大学“青年科学家培育计划”。

摘　　要：目的采用网络药理学和分子对接的方法研究二至丸治疗更年期高血压的作用机制。方法利用中药系统药理学数据库和分析平台筛选二至丸的有效成分及靶点,通过Uniprot数据库将靶点名称校正为标准的基因名。通过GeneCards和Online Mendelian Inheritance in Man(OMIM)数据库检索更年期高血压的疾病靶点,通过韦恩图得到交集靶点。运用Cytoscape软件构建“药物-有效成分-交集靶点”网络,采用STRING数据库构建蛋白质相互作用网络,并进行聚类分析。运用DAVID数据库进行GO和KEGG富集分析,通过Cytoscape3.7.1软件构建“药物-成分-靶点-通路”图。通过Autodock vina软件对筛选的靶点和有效成分进行分子对接验证。结果经筛选得到二至丸中有效成分共23个,其靶点共192个,疾病靶点1189个,取交集后获得126个靶点。根据GO和KEGG富集分析,涉及的主要生物过程有细胞增殖和凋亡、对一氧化氮生成的正调控等,主要通路包括Toll样受体信号通路、TNF信号通路、NOD样受体信号通路和MAPK信号通路等。分子对接显示MAPK1、RELA、AKT1与槲皮素、木犀草素、山柰酚有较高的结合活性。结论二至丸中可能主要通过抗炎、抗氧化、抗平滑肌增殖等作用来改善血压水平。Objective To explore the mechanism of Erzhi pill in the treatment of hypertension based on network pharmacology and molecular docking.Methods Traditional Chinese medicine systems pharmacology database and Analysis platform was used to screen the main active ingredients and targets of Erzhi pill.And Uniprot database was used to convert target names to standard gene names.By means of Gene Cards and Online Mendelian Inheritance in Man(OMIM),targets of menopausal hypertension were collected.The intersecting targets were obtained by using the Venn map.The Cytoscape software was used to construct the“drug-active ingredient-intersection target”network,and STRING online database was used to build protein-protein interactions Network,and conduct cluster analysis.DAVID database was used to perform GO function enrichment analysis and KEGG pathway enrichment analysis.A“drug-ingredient-target-pathway”network was constructed by Cytoscape 3.7.1 software.Autodock vina software was used to conduct molecular docking between targets and active ingredients in the“drug-ingredient-target-pathway”network.Results A total of 23 active ingredients in Erzhi Pills were screened,with a total of 192 targets and 1189 disease targets.After the intersection,126 targets were obtained.According to GO and KEGG enrichment analysis,the main biological processes involved include cell proliferation and apoptosis,positive regulation of nitric oxide production,etc.The main pathways include Toll-like receptor signaling pathway,TNF signaling pathway,and NOD-like receptor signaling pathway and MAPK signaling pathway.Molecular docking showed that MAPK1,RELA,AKT1 have high binding activity with quercetin,luteolin and kaempferol.Conclusion Erzhi pills may improve blood pressure levels mainly through anti-inflammatory,anti-oxidant,and anti-smooth muscle proliferation effects.

关 键 词：二至丸 更年期高血压 网络药理学 分子对接 作用机制 

分 类 号：R285.6[医药卫生—中药学]