摘要
目的采用网络药理学的方法探究芪参益气滴丸治疗心肌梗死(MI)的药理作用机制。方法使用中药系统药理学数据库及分析平台(TCMSP)检索芪参益气滴丸中药复方中四味草药的所有活性化合物成分和作用靶点;通过OMIM、TTD、PharmG KB、DisG inN ET及DrugB ank数据库对MI的相关疾病靶点进行检索,并与药物的治疗靶点进行映射,获得药物作用于疾病的靶点。用Cytoscape软件构建药物成分-疾病靶点网络,筛选药物治疗心肌梗死的核心靶点。利用DAVID数据库进行KEGG富集分析,Omicshare数据库进行GO二级分类富集并对KEGG富集的结果进行可视化处理。结果选择口服生物利用度(OB)≥30%,类药性(DL)≥0.18,肠上皮细胞膜渗透性(Caco-2)≥-0.4及半衰期(HL)≥4 h作为活性化合物的ADME筛选条件,共获得82个活性成分和610个成分靶点。五个疾病数据库共检索MI相关靶点1 713个,药物靶点映射到疾病中共获得103个靶点。对大于平均度值的27个核心靶点进行DAVID富集分析,发现ADRB2、CHRM3、CHRM2、NOS3、NOS2、ADRA1D、CALM1、PIK3CG、DRD1、PDE3A、F2、GSK3B、COX2、ESR2、ACHE、SCN5A、COX1、PTGS2等18个芪参益气滴丸治疗MI的核心靶点富集到钙信号通路、cA MP信号通路、cG MP-PKG信号通路等19条与MI相关的通路。结论通过使用系统药理学的理论和方法证实了芪参益气滴丸多成分、多靶点、多途径的治疗特点,预测了其治疗MI的可能机制,为其基础研究提供了参考和理论依据。
Objective To explore the pharmacological mechanism of Qishen Yiqi dropping pills in the treatment of myocardial infarction(MI) by network pharmacology. Methods The Chinese medicine system pharmacology database and analysis platform(TCMSP) was used to search for all active compound components and targets of the four herbs in the Chinese herbal compound of Qishen Yiqi dropping pills. The targets of myocardial infarction were collected by OMIM, TTD, PharmGKB, DisGinNET and DrugBank databases. Then disease targets were merged with the therapeutic targets of the drug to obtain the targets of the drug for the disease. The drug components-disease targets network was constructed by Cytoscape software, and the core targets of the drug for treating myocardial infarction were filtrated by analyzing the network. The DAVID database performed KEGG enrichment analysis, and the Omicshare database performed GO secondary classification enrichment and visualized the results of KEGG enrichment. Results Oral bioavailability(OB)≥30%, drug-likeness(DL)≥0.18, Caco-2 permeability(Caco-2)≥-0.4 and half-life(HL)≥4 h were chosen as the active compounds ADME screening conditions. A total of 82 active components and 610 component targets were obtained. Five disease databases were used to search for myocardial infarction targets and a total of 1 713 related targets were obtained. Then 103 targets were mapped to the drug targets successfully. DAVID enrichment analysis was performed on 27 core targets greater than the average degree, and ADRB2, CHRM3, CHRM2, NOS3, NOS2, ADRA1 D, CALM1, PIK3 CG, DRD1, PDE3 A, F2, GSK3 B, COX2, ESR2, ACHE, SCN5 A, COX1, PTGS2,18 genes were the core targets for myocardial infarction, which were enriched in 19 pathways related to myocardial infarction, such as calcium signaling pathway, cAMP signaling pathway, and cGMP-PKG signaling pathway. Conclusion The theory and method of systemic pharmacology confirm the multi-components, multi-targets and multi-pathways treatment characteristics of Qishen Yiqi dropping pills, and predict its possible mechanism for treating MI, which provide reference and theory for the basic research of the disease simultaneously.
作者
魏欣
周仁鹏
刘清武
胡伟
鲁超
Wei Xin;Zhou Renpeng;Liu Qingwu(Dept of Clinical Pharmacology Center,The Second Hospital of Anhui Medical University,Hefei 230601;Tianjin Tasly Pharmaceutical Co.Ltd.,Tianjin 300402)
出处
《安徽医科大学学报》
CAS
北大核心
2021年第2期194-201,共8页
Acta Universitatis Medicinalis Anhui
基金
安徽省自然科学基金(编号:1908085QH317)
安徽医科大学第二附属医院国家自然科学基金孵化计划(编号:2019GMFY03)。
关键词
芪参益气滴丸
心肌梗死
网络药理学
靶点
信号通路
Qishen Yiqi dropping pills
myocardial infarction
network pharmacology
targets
signaling pathways
