基于基因表达综合数据库临床队列及分子对接验证银杏叶治疗冠状动脉粥样硬化性心脏病的网络药理学研究  

A network pharmacology study on Yinxingye in the treatment of coronary heart disease based on GEO clinical cohort and molecular docking validation

作　　者：刘惠婷 林珺尧 王宇 陈铭瑜 陈敏[4] 高红瑾[4] LIU Huiting

机构地区：[1]福建医科大学药学院,福建福州350004 [2]广西中医药大学赛恩斯新医药学院,广西南宁530200 [3]福建中医药大学药学院,福建福州350122 [4]福建医科大学省立临床医学院/福建省立医院药学部,福建福州350001

出　　处：《中医临床研究》2025年第1期8-14,共7页Clinical Journal Of Chinese Medicine

摘　　要：目的:结合网络药理学、分子对接和基因表达综合数据库(GEO)临床队列验证的方法研究银杏叶治疗冠状动脉粥样硬化性心脏病(简称冠心病)的分子机制。方法:检索中药系统药理学数据库与分析平台(TCMSP),获取银杏叶活性成分及靶点。通过GeneCards、在线人类孟德尔遗传数据库(OMIM)获取冠心病靶点,采用Cytoscape构建银杏叶治疗冠心病活性成分–靶点网络图。将靶点蛋白导入STRING数据库,构建蛋白质–蛋白质相互作用网络,并进行拓扑分析,筛选出银杏叶治疗冠心病的核心靶点。通过AutoDock Tools和Vina软件对关键活性成分和关键靶点进行分子对接。最后通过GEO的GSE20681数据集进行临床队列分析,获得冠心病患者与对照组患者在核心靶点mRNA表达方面的差异。结果:获得银杏叶治疗冠心病的活性成分14个、作用靶点42个。通过网络拓扑分析筛选到13个核心靶点。银杏叶治疗冠心病的关键活性成分为槲皮素、山柰酚、木犀草素、异鼠李素、豆甾醇,度值居前5位的关键靶点为白细胞介素(Interleukin,IL)–6、IL–10、基质金属蛋白酶(Matrix Metalloproteinase,MMP)9、过氧化物酶体增殖物激活受体γ(Peroxisome Proliferator Activated Receptor Gamma,PPARG)和C–C基序趋化因子配体2(Chemokine C–C Motif Ligand 2,CCL–2),分子对接证明关键活性成分与关键靶点结合活性良好。通过GEO GSE20681数据集验证MMP9在冠心病患者中的表达显著高于对照组患者(P=0.002)。结论:研究揭示了银杏叶的多个活性成分通过MMP9介导的多个通路发挥抗冠心病效应,为进一步探索银杏叶治疗冠心病的分子机制及临床合理使用银杏叶提取物提供理论基础。Objective:To study the molecular mechanism of Yinxingye(Ginkgo Folium)in the treatment of coronary heart disease by network pharmacology,molecular docking and GEO clinical cohort verification.Methods:Relevant data on TCMSP was searched to obtain the effective components and targets of Yinxingye.GeneCards and OMIM were used to obtain coronary heart disease targets,and Cytoscape was used to construct a network diagram of effective components-target of Yinxingye in the treatment of coronary heart disease.The target proteins were imported into STRING database to construct a protein-protein interaction network,and topological analysis was performed to screen out the core targets of Yinxingye in the treatment of coronary heart disease.Molecular docking of key effective components and key targets was performed by AutoDock Tools and Vina software.Finally,the GSE20681 data set of GEO was used for clinical cohort analysis to gain differences in core target gene mRNA expressions of coronary heart disease patients and patients in the control group.Results:There were 14 effective components and 42 targets of Yinxingye in the treatment of coronary heart disease.The network topology analysis identified 13 core targets.The key effective components of Yinxingye in the treatment of coronary heart disease were quercetin,kaempferol,luteolin,isorhamnetin,and stigmasterol,and the top five key targets in degree value were IL-6,IL-10,MMP9,PPARG and CCL-2.The molecular docking proved that the key effective components had good binding activity with the key targets.The GSE20681 data set of GEO verified that the expression of MMP9 in coronary heart disease patients was significantly higher than that in the control group(P=0.002).Conclusion:The study reveals that multiple effective components of Yinxingye exert anti-coronary heart disease effect through multiple pathways mediated by MMP9,which provides a theoretical basis for further exploring the molecular mechanism of Yinxingye in the treatment of coronary heart disease and the clinical ra

关 键 词：网络药理学 分子对接 银杏叶 冠状动脉粥样硬化性心脏病 生物信息学 

分 类 号：R256.2[医药卫生—中医内科学]