摘要
目的:从分子水平探究黄芪-丹参中药配伍抗急性心肌梗死作用机制,预测心肌梗死气虚血瘀证潜在靶点及通路。方法:采用中医药整合药理学研究平台(integrative pharmacology-based research platform of traditional chinese medicine,TCMIP)V2.0,检索并获取黄芪和丹参活性成分、靶标及心肌梗死靶标信息,借助平台构建中药-成分-靶点-通路多维分析,对药物干预疾病的关键靶点进行富集分析,最后得出蛋白质相互作用网络(protein-protein interaction network,PPI);同时通过基因本体数据库(gene ontology,GO)功能分析和京都基因与基因组百科全书库(kyoto encyclopaedia of genes and genomes,KEGG)通路富集分析,预测黄芪-丹参药物组合抗急性心肌梗死的分子机制。结果:丹参黄芪共筛选出123个活性成分,其中丹参96个,黄芪27个,筛选出心肌梗死相关靶标1063个,这些活性成分通过联合调控白介素(interleukin,IL)、肿瘤域突变体、卵巢肿瘤结构域蛋白酶、一氧化氮合成酶(endothelial nitric oxide synthase,eNOS)、转化生长因子-β(transforming growth factor-β,TGF-β)、激酶非活性BamHI-A区域的早期基因(bamhi-a rightward openreading frame,BRAF)等靶标,直接或间接参与炎症信号通路、雌激素信号通路等,进而发挥抗心肌梗死的作用。结论:通过整合药理学策略分析,揭示了黄芪-丹参药对组合能够多途径有效抗心肌梗死作用的分子机制。
Objective:To explore the anti-acute myocardial infarction(AMI)mechanism of Astragalus-Salvia miltiorrhiza at the molecular level,and to predict the potential targets and pathways of myocardial infarction with Qideficiency and blood-stasis syndrome.Methods:The Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP)V2.0 was used to retrieve and obtain information on the active ingredients,targets,and myocardial infarction targets of Astragalus and Salvia miltiorrhiza.The platform was used to construct a multi-dimensional analysis of traditional Chinese medicine-components-targets-pathways,and enrichment analysis was performed base on the key targets of drug intervention in diseases.Finally,the protein-protein interaction network(PPI)was obtained;at the same time,Gene Ontology database(GO)functional analysis and Kyoto Encyclopaedia of Genes and Genomes(KEGG)pathway enrichment analysis were used to predict the molecular mechanism of Astragalus-Salvia miltiorrhiza drug combination against acute myocardial infarction.Results:A total of 123 active ingredients were screened out from Astragalus and Salvia miltiorrhiza,including 96 from Salvia miltiorrhiza and 27 from Astragalus membranaceus.A total of 1063 targets related to myocardial infarction were selected.These active ingredients jointly regulate interleukin(IL),tumor domain mutants,ovarian tumor domain protease,endothelial nitric oxide synthase(eNOS),transforming growth factor-β(TGF-β)and BamHI-A Rightward openreading Frame(BRAF),directly or indirectly participate in inflammatory signaling pathways,estrogen signaling pathways,etc.,and thus play an anti-myocardial infarction effect.Conclusion:Through the analysis of integrated pharmacological strategy,the molecular mechanism of Astragalus-Salvia miltiorrhiza combination can effectively prevent myocardial infarction in multiple ways.
作者
刘志超
陈金红
高晟玮
马莉
王治中
陆安民
王保和
谷旭放
LIU Zhi-cao;CHEN Jin-hong;GAO Sheng-wei;MA Li;WANG Zhi-zhong;LU An-min;WANG Bao-he;GU Xu-fang(Tianjin University of Traditional Chinese Medicine,Tianjin,300193;Second Affiliated Hospital of Tianjin University of TCM,Tianjin 300150)
出处
《中国中医基础医学杂志》
CAS
CSCD
北大核心
2021年第10期1644-1648,共5页
JOURNAL OF BASIC CHINESE MEDICINE
基金
国家自然科学基金资助项目(81873149)-基于CDKN2A通路的益气活血法治疗心肌梗死恢复期气虚血瘀证表观遗传调控研究。
关键词
整合药理学
黄芪-丹参
心肌梗死
机制
Integrated pharmacology
Astragalus-Salvia miltiorrhiza
Myocardial infarction
Mechanism
