通脉降浊方治疗冠状动脉粥样硬化性心脏病不稳定性心绞痛作用机制的网络药理学分析

A network pharmacology analysis of the action mechanism of the Tongmai Jiangzhuo prescription on unstable angina pectoris of coronary heart disease

目的:基于网络药理学分析通脉降浊方治疗冠状动脉粥样硬化性心脏病(简称冠心病)不稳定性心绞痛的作用机制。方法:借助中药系统药理学数据库与分析平台(TCMSP)检索通脉降浊方的有效成分,并将有效成分转换为靶点信息。于GeneCards数据库检索冠心病不稳定性心绞痛的靶点信息,利用Cytoscape软件构建药物-活性成分-关键靶点”网络,从STRING平台生成蛋白质-蛋白质相互作用网络,在Metascape数据库进行基因本体论(GO)分析与京都基因和基因组数据库(KEGG)通路富集分析。结果:获得272个有效成分,249个药物靶点,619个疾病靶点,86个交集靶点。蛋白质-蛋白质相互作用网络关键靶点为丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、白细胞介素-6(Interleukin-6,IL-6)、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素-1β(Interleukin-1 Beta,IL-1B)、基质金属蛋白酶9(Matrix Metallopeptidase 9,MMP9)、CC类趋化因子配体2(C-C Motif Chemokine Ligand 2,CCL2)。GO分析主要为对脂多糖的反应、细胞成分运动的正调控、对氧气水平的反应、对有毒物质的反应、活性氧代谢过程、血液循环等,KEGG通路富集分析主要为糖尿病并发症中的晚期糖基化终末产物-晚期糖基化终末产物受体信号通路、癌症途径、肿瘤坏死因子信号通路、缺氧诱导因子1信号通路、丙型肝炎、蛋白聚糖在癌症中的作用。结论:本研究初步明确通脉降浊方的多种有效成分作用于冠心病不稳定性心绞痛的多个疾病靶点与通路,体现了中药多靶点、多通路的特点,为进一步的实验研究提供思路。

Objective:To analyze the action mechanism of the Tongmai Jiangzhuo prescription(通脉降浊方)on unstable angina pectoris of coronary heart disease based on network pharmacology.Methods:The effective components of the Tongmai Jiangzhuo prescription were retrieved in TCMSP database,and were transformed into targets information.The“medicine-active ingredients-key targets”network was constructed by Cytoscape software,and the PPI network was obtained by STRING platform.The GO enrichment analysis and KEGG pathway enrichment analysis were performed by Metascape database.Results:A total of 272 active ingredients were obtained,with 249 medicine targets,619 disease targets and 86 intersection targets.The key targets of PPI network were AKT1,IL6,VEGFA,TNF,IL-1B,MMP9 and CCL2.The Go analysis mainly included the response to lipopolysaccharide,positive regulation of cell component movement,response to oxygen level,response to toxic substances,active oxygen metabolism process,blood circulation,etc..The KEGG pathway enrichment analysis mainly included AGE-RAGE signal pathway in diabetic complications,cancer pathway,TNF signal pathway,hypoxia inducible factor 1 signal pathway,hepatitis C,and the role of proteoglycan in cancer.Conclusion:This study preliminarily confirmed that the various effective components of the Tongmai Jiangzhuo prescription on multiple disease targets and pathways of unstable angina pectoris,reflecting the characteristics of multiple targets and multi-pathways of TCM medicine,and providing more ideas for further experimental research.