摘要
目的:运用网络药理学与生物信息学方法挖掘黄山药治疗冠心病的作用靶点和相关信号通路,探究其作用机制,为冠心病的临床治疗提供理论基础。方法:本研究从基因表达集(GEO)数据库筛选出冠心病的疾病靶基因,通过搜寻中国知网、万方、VIP数据库及查找目前报道的化学成分获得黄山药有效的活性成分及预测靶基因,将两者取交集得到药物-疾病蛋白靶基因,并通过Cytoscape软件将结果进行网络化展示,通过网络拓扑算法筛选出作用的关键靶基因,运用集成发现数据库(DAVID)在线工具对关键靶基因进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,结合相关文献分析黄山药治疗冠心病的作用机制。结果:黄山药所含活性成分8个,预测靶点203个;通过疾病数据库检索与冠心病发生发展相关的已知疾病靶点3729个;共同靶点21个,预测EGFR、PTGS2、JUN、MAPK9、NFKB2等蛋白可能是黄山药治疗冠心病的关键靶点;GO富集分析得到了37个条目,黄山药可能通过调控炎症因子、表皮生长因子、细胞凋亡作用治疗冠心病;KEGG通路富集分析明确了12条信号通路,其中信号通路包括花生四烯酸代谢、ErbB信号通路、MAPK信号通路等。结论:黄山药治疗冠心病具有多靶点、多途径的特性,其所作用的多条信号通路存在直接或间接关联性,参与表皮生长因子、炎症、凋亡机制等方面,并对血管内皮、心肌细胞等多方位综合干预而发挥药效,其疗效机制与多因素所诱导的冠心病的病理机制相吻合。
Objective:To explore the targets and related signaling pathways of Huangshanyao in the treatment of coronary heart disease(CHD)and explore its mechanism of action by network pharmacology and bioinformatics,to provide fundamental basis for clinical application.Method:The disease target genes of CHD were screened from the gene expression set(GEO)database.The effective active components and predicted target genes of Huangshanyao were obtained by searching the databases of CNKI,Wanfang and VIP,and the reported chemical components.The drug-disease-protein target genes were obtained by intersection of the two sets,and the results were displayed on the network through Cytoscape software.The key target genes were screened by topological algorithm,and the gene ontology(GO)analysis and Kyoto Encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of key target genes were carried out using the integrated discovery database(David)online tool.Combined with the relevant literature,the mechanism of Huangshanyao in the treatment of CHD was analyzed.Result:Huangshanyao contained 8 active ingredients and 203 predictive targets.3729 known disease targets related to the occurrence and development of CHD were searched through the disease database.21 common targets were got.EGFR,PTGS2,JUN,MAPK9,NFKB2 may be the key targets proteins of Huangshanyao in the treatment of CHD.GO enrichment analysis had obtained 37 entries.Huangshanyao may treat CHD by regulating inflammatory factors,epidermal growth factor and cell apoptosis.KEGG pathway enrichment analysis identified 12 signaling pathway including arachidonic acid metabolism,ErbB signaling pathway,MAPK signaling pathway,etc.Conclusion:The treatment of CHD with Huangshanyao has the characteristics of multi-target,multi-channel.There are direct or indirect correlations among the signal pathways.It participates in the mechanism of epidermal growth factor,inflammation and apoptosis,and plays a role in the comprehensive intervention of vascular endothelium and myocardial cells.The curative effect mechanism is consistent with the pathological mechanism of CHD induced by multiple factors.
作者
刘思莉
李小芬
王涛
梁纪懿
刘宏林
瞿礼萍
邹文俊
LIU Si-li;LI Xiao-fen;WANG Tao;LIANG Ji-yi;LIU long-lin;QU Li-ping;ZOU Wen-jun(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Key Laboratory of Standardization for Chinese Herbal Medicine,Ministry of Education,National Key Laboratory Breeding Base of Systematic Research,Development and Uilization of Chinese Medicine Resources,Chengdu 611137,Sichuan)
出处
《中药与临床》
2021年第3期50-55,61,共7页
Pharmacy and Clinics of Chinese Materia Medica
关键词
黄山药
冠心病
表皮生长因子
炎症
凋亡
Huangshanyao
coronary heart disease
epidermal growth factor
inflammation
apoptosis
作者简介
刘思莉(1994-),女,硕士研究生在读,从事中药基础理论及应用研究,Tel:15828077602,Email:1339009467@qq.com;通讯作者:邹文俊(1966-),女,教授,从事中药基础理论及应用研究,Email:zouwenjun@163.com。
