基于网络药理学的刺芒柄花素抗颈动脉粥样硬化斑块的作用靶点及机制  

Targets and mechanism of the anti-carotid atherosclerotic plaque effect of formononetin:a study based on network pharmacology

作　　者：李珊[1,2] 赵康 杨提 王莹 邓生琼 LI Shan;ZHAO Kang;YANG Ti;Wang Ying;DENG Shengqiong(School of Public Health,Hubei University of Medicine,Shiyan 442099,Hubei Province,China;Department of Clinical Laboratory,Gongli Hospital of Shanghai Pudong New Area,Shanghai 200025,China)

机构地区：[1]湖北医药学院公共卫生与健康学院,湖北十堰442099 [2]上海市浦东新区公利医院检验科,上海200135

出　　处：《同济大学学报（医学版）》2024年第1期24-30,共7页Journal of Tongji University(Medical Science)

基　　金：上海市中西医结合学会管理专业委员会“医院管理研究项目”(2023-YYGL19);上海市浦东新区卫生健康委员会学科带头人培养计划(PWRd2020-10)。

摘　　要：目的 利用网络药理学方法联合GEO基因芯片数据及分子对接技术探索刺芒柄花素治疗颈动脉粥样硬化斑块的潜在分子作用机制。方法 在PubChem等数据库获取刺芒柄花素的作用靶点,在GeneCards、DisGeNET等数据库获取颈动脉粥样硬化斑块相关靶点基因,与GEO芯片筛选的差异基因合并去重后得到颈动脉粥样硬化斑块靶点基因;通过构建韦恩图,得到药物与疾病共有靶点;利用R软件包对共有靶点进行富集分析;利用String在线平台构建共有靶点蛋白互作网络,运用Cytoscape软件对网络进行拓扑学参数筛选得到核心靶点;再运用分子对接技术将筛选出来的核心靶点分别与刺芒柄花素的结合活性进行验证。结果 筛选出413个刺芒柄花素作用靶点及1 244个颈动脉粥样硬化斑块表达差异基因,两者取交集后得到55个刺芒柄花素干预颈动脉粥样硬化斑块的潜在靶点,KEGG富集分析显著富集于PPAR信号通路、MAPK信号等通路,并显示基因功能与炎症及细胞凋亡相关;运用Cytoscape筛选得到核心靶点CAP1、CXCL8、EGFR、FOS、CTSS、IGF1、MMP9、PPARG;分子对接模拟验证显示,CAP1、CXCL8、EGFR、FOS、IGF1、MMP9、PPARG等核心靶点与刺芒柄花素结合强,有较好的结合活性。结论 刺芒柄花素作用于CAP1等多个核心靶点调节炎症相关信号通路,进而发挥抗动脉斑块形成的作用,可为后续临床用药提供数据支持。Objective To explore the potential targets and mechanism of formononetin in the treatment of atherosclerotic plaque treatment based on network pharmacological study.Methods The target genes of formononetin were obtained from PubChem and other databases;the target genes of carotid atherosclerotic plaques were obtained from GeneCards and DisGeNET databases,then screened and combined with those extracted from GEO gene chip.The target genes shared by the drug and the disease were obtained through Venn diagrams and enriched by R software package.The protein interactions network of the shared targets was constructed by String online platform,and the core targets were obtained by screening the topological parameters of the network with Cytoscape software;the binding activities of the screened core targets with formononetin were verified by molecular docking technology.The core targets of CAP1,CXCL8,EGFR,FOS,KDR,IGF1,MMP9,and PPARG were screened,and the molecular docking simulation showed that these core targets had strong binding activities with formononetin.Results A total of 413 action targets of formononetin and 1 244 differentially expressed genes in carotid atherosclerotic plaque were screened out.Based on the interaction analysis,55 potential targets related to the effect of formononetin on carotid atherosclerotic plaques were obtained.KEGG enrichment analysis showed that the genes were significantly enriched in PPAR signaling pathway,MAPK signaling and other pathways,and the gene-function were mostly related to inflammation and apoptotic cells.The core targets CAP1,CXCL8,EGFR,FOS,CTSS,IGF1,MMP9 and PPARG were obtained by Cytoscape screening,and the molecular docking simulation showed that their core targets had strong binding activities with formononetin.Conclusion Formononetin acts on multiple core targets such as CAP1 to regulate inflammation-related signaling pathways,thereby exerting an effect on preventing the arterial plaque formation,which provides support for subsequent clinical drug development.

关 键 词：网络药理学 GEO数据库 刺芒柄花素 动脉粥样硬化斑块 

分 类 号：R961.1[医药卫生—药理学] R915[医药卫生—药学]