基于网络药理学和分子对接探讨益气复脉汤治疗冠心病的作用机制  

Study on the Mechanism of YiQiFuMai Decoction in Treating Coronary Heart Disease based on Network Pharmacology Molecular Docking

作　　者：王镕 况春燕[2] WANG Rong;KUANG Chunyan(Guizhou University of Traditional Chinese Medicine,Guiyang Guizhou 550025;Department of Cardiology,Guizhou Provincial People's Hospital,Guiyang Guizhou 550003)

机构地区：[1]贵州中医药大学,贵州贵阳550025 [2]贵州省人民医院心内科,贵州贵阳550003

出　　处：《内蒙古中医药》2024年第12期164-168,共5页Inner Mongolia Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(No.81560056);贵州省第十二批优秀青年科技人才项目(黔科合平台人才[2019]5662);贵州省科技计划项目(黔科合基础[2018]1097);贵州省留学人员科技活动择优资助项目(黔人项目资助合同[2018]0003号);贵州省科技平台及人才团队计划项目(黔科合平台人才2017-5405)。

摘　　要：目的:以网络药理学为研究手段与分子对接相结合研究益气复脉汤(YiQiFuMai decoction,YQFM)对于冠心病(coronary heart disease,CHD)的生物学作用、关键靶点及潜在药理机制等。方法:本文运用网络药理学方法,从TCMSP、SyMmap数据库与文献中获得中药活性成分,Metascape数据库中获取CHD的靶点,并将二者取交集,对交集靶点进行GO、KEGG富集分析。利用STRING 11.5数据库对交集靶点进行蛋白互作(PPI)网络分析,在Cytoscape 3.10.1软件绘制药物-成分-靶点-疾病-通路图并使用Cytohubba、CytoNCA筛选出的YQFM治疗CHD的核心靶点,并与核心成分进行分子对接技术验证。结果:从YQFM中筛选得到豆甾醇、山柰酚、β-谷甾醇、异鼠李素、柳穿鱼素、隐品碱、芝麻素、灌木远志酮A、常春藤皂苷元、戈米辛R为治疗CHD的核心成分;核心靶点为IL6、AKT1、TP53、STAT3、EGFR、TNF、IL1B等,GO分析结果为6340个生物过程,549个细胞组分,和1122个分子功能;KEGG分析得到287条通路。本研究利用药理学方法探讨治疗YQFM的药理基础与作用机制,运用分子对接验证YQFM中核心成分与核心靶点的亲和力;β-谷甾醇与AKT1、TP53对接的结合能分别为-6.2 kcal/mol、-6.0 kcal/mol,常春藤皂苷元与AKT1对接的结合能分别为-7.6 kcal/mol,豆甾醇于TP53对接的结合能为-7.1 kal/mol。结论:YQFM治疗CHD可能通过IL-17、HIF-1、JAKSTAT、TNF等信号通路作用于IL6、AKT1、TP53、STAT3、EGFR、TNF、IL1B等靶蛋白的表达起到促进细胞生长发育,调节血压、血脂与动脉粥样硬化,抗血栓,稳定粥样斑块,保护血管内皮细胞,缓解炎症反应、氧化应激反应、调控细胞的凋亡等方面治疗CHD。Objective:To study the biological effect,key targets and potential pharmacological mechanisms of YiQiFuMai doction(YQFM)on coronary heart disease(CHD)using network pharmacology as a research method comhined with molecular docking.Methods:In this pa-per,network pharmacology methods were used to obtain active ingredients of traditional Chinese medicine from TCMSP,SyMmap datahases and literature,and CHD targets were obtained from Metascape datahase,and the intersection of the two was taken,and GO and KEGG en-richment analysis were carried out on the intersection targets.The STRINGI1.5 database was used to conduct protein interaction(PPI)net-work analysis on intersection targets,and a drug-component-target-disease-pathway map was drawn in Cytoscape 3.10.1 software,and the core targets of YQFM for treating CHD selected by Cytohubba and CytoNCA were used to verify the molecular docking technology with the core components.Results:Screening from YQFM showed that stigmasterol,kaempferol,beta-sitosterol,isorhamnetin,wiltchinin,cryptopine.sesamin,shrub polygalone A,hederagenin,and gomisin R are the core components in the treatment of CHD;the core targets are IL6,AKT1.TP53,STAT3,ECFR,TNF,IL1B,etc.The GO analysis results showed 6340 biological processes,549 cell components,and 1122 molecular functions;KEGG analysis resulted in 287 pathways.In this study,pharmacological methods were used to explore the pharmacological basis and mechanism of action for treating YQFM,and molecular docking was used to verify the affinity between the core components and the core target in YQFM;the binding energies ofβ-sitosterol docking with AKT1 and TP53 were-6.2kcal/mol and-6.0kcal/mol,respectively,the binding energies of hederagenin docking with AKT1 were-7.6kcal/mol,respectively,and the binding energy of stigmasterol docking with TP53 was-7.1kal/mol.Conclusion:YQFM treatment of CHD may promote cell growth and development through signaling pathways such as IL-17,HIF-1,JAKSTAT,and TNF on the expression of target proteins such as IL6,AKT1,TP53,S

关 键 词：益气复脉汤 冠心病 网络药理学 分子对接 

分 类 号：R541.4[医药卫生—心血管疾病]