基于网络药理学探讨桂枝生姜枳实汤治疗冠心病不稳定型心绞痛的作用机制

Investigation on the action mechanism of Guizhi Shengjiang Zhishi Decoction in the treatment of unstable angina of coronary heart disease based on network pharmacology

目的 利用网络药理学方法分析桂枝生姜枳实汤治疗冠心病不稳定型心绞痛(UA)的药物成分、作用靶点及潜在机制。方法 利用TCMSP数据库筛选桂枝生姜枳实汤的药物成分及作用靶点,应用GeneCards、PharmGkb、DrugBank数据库筛选UA的疾病靶点,对桂枝生姜枳实汤治疗UA的共有靶标进行整合,采用Cytoscape 3.8.0软件构建“药物-成分-靶点”网络图,运行STRING平台进行靶蛋白相互作用(PPI)分析,运用R语言软件进行基因本体功能富集(GO)与京都基因与基因组百科全书(KEGG)富集分析,分析其潜在作用机制。结果 共筛选桂枝生姜枳实汤有效成分34种,涉及靶标139个。“药物-成分-靶点”图中筛选出交集基因77个,其干预的PPI网络主要涉及PTSG2、HSP90AA1、PTGS1等关键基因,拓扑分析后发现TP53、MAPK3、MAPK1、AKT1、ESR1、JUN可能为核心靶标。GO及KEGG富集分析结果显示桂枝生姜枳实汤干预UA主要涉及活性氧代谢过程、氧化应激反应、泛素样蛋白连接酶结合、转录因子活性等多种生物学途径以及PI3K-Akt、IL-17、HIF-1、p53等信号通路。结论 桂枝生姜枳实汤对UA具有治疗作用,其潜在机制为激活PI3K-Akt、IL-17、HIF-1、p53等信号通路,调节TP53、MAPK3、MAPK1、AKT1、ESR1、JUN等靶基因,改善缺氧所致心肌损伤,从而达到干预UA的作用。

Objective To investigate the drug components,action targets and potential mechanism of Guizhi Shengjiang Zhishi Decoction in the treatment of unstable angina(UA)of coronary heart disease according to the network pharmacology method.Methods TCMSP database was used to screen the drug components and action targets of Guizhi Shengjiang Zhishi Decoction,GeneCards,PharmGkb and DrugBank databases were used to screen the disease targets of UA,and the common targets of Guizhi Shengjiang Zhishi Decoction in the treatment of UA were integrated.The network diagram of"drugs-components-targets"was constructed by using Cytoscape 3.8.0 software.STRING platform was run to analyze the protein-protein interaction(PPI),and R language software was used to conduct the enrichment analysis of gene ontology(GO)and Kyoto encyclopedia of genes and genomics(KEGG)to analyze its potential mechanism.Results A total of 34 effective components of Guizhi Shengjiang Zhishi Decoction were screened,involving 139 targets.A total of 77 overlapping genes were screened from the"drugs-components-targets"diagram,and the PPI network of its intervention mainly involves key genes such as PTSG2,HSP90AA1 and PTGS1.After topological analysis,it was found that TP53,MAPK3,MAPK1,AKT1,ESR1 and JUN might be the core targets.The results of GO and KEGG enrichment analysis showed that the intervention of Guizhi Shengjiang Zhishi Decoction on UA mainly involved a variety of biological pathways such as active oxygen metabolism process,oxidative stress reaction,ubiquitin-like protein ligase binding,transcription factor activity,and PI3K-Akt,IL-17,HIF-1,p53 and other signal pathways.Conclusion Guizhi Shengjiang Zhishi Decoction has therapeutic efficacy on UA,and its potential mechanism is to activate PI3K-Akt,IL-17,HIF-1,p53 and other signal pathways,regulate TP53,MAPK3,MAPK1,AKT1,ESR1,JUN and other target genes,and improve myocardial injury caused by hypoxia,so as to achieve the efficacy of intervention on UA.