基于网络药理学研究川芎嗪治疗冠心病分子机制

Molecular Mechanism of Ligustrazine in the Treatment of Coronary Heart Disease Based on Network Pharmacology

目的通过网络药理学方法探讨川芎嗪治疗冠心病的分子机制。方法利用Pharmmapper数据库、中药分子机制生物学分析平台(BATMAN-TCM)预测化合物靶点,通过与人类基因数据库(Genecards)、在线人类孟德尔遗传数据库(OMIM)治疗冠心病的相关靶点进行匹配,得到化合物-疾病共同靶蛋白。利用Cytoscape3.7.1软件构建化合物-靶点网络,然后借助STRING数据库进行蛋白互作网络分析,最后利用R语言进行基因本体(gene ontology,GO)富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果经过筛选得到川芎嗪作用于冠心病的靶点115个,这些靶点主要富集在磷脂酰肌醇3激酶/蛋白激酶B(phosphatidylinositol 3 kinase/protein kinase B,PI3K-Akt)、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等多条信号通路上。结论川芎嗪可能主要通过抗凋亡、抗凝血、抗炎、促进血管新生、应对缺氧等多方面对冠心病进行干预,体现了中药多靶点、多通路的作用特点。

Objective To explore the molecular mechanism of ligustrazine in the treatment of coronary heart disease by means of network pharmacology.Methods The compound targets were predicted by Pharmmapper and BATMAN-TCM databases,and the compound-disease common targets were obtained by matching with the related targets of Genecards and OMIM database in the treatment of coronary heart disease.The compound-target network was constructed by Cytoscape3.7.1 software,and the protein interaction network was analyzed by STRING database.Finally,GO enrichment analysis and KEGG pathway enrichment analysis were carried out by using R language.Results Through screening,115 targets of ligustrazine on coronary heart disease were obtained.These targets are mainly concentrated in phosphatidylinositol 3 kinase/protein kinase B(PI3K-Akt),hypoxia inducible factor-1(HIF-1),mitogen activated protein kinase(MAPK)and other signal pathways.Conclusion Ligustrazine interfere with coronary heart disease mainly through anti-apoptosis,anti-coagulation,anti-inflammation,promoting angiogenesis,coping with hypoxia and other aspects,reflecting the characteristics of multi-target and multipathway of traditional Chinese medicine.