基于网络药理学与分子对接探究麻黄细辛附子汤治疗病态窦房结综合征的作用机制  

Exploration of the mechanism of action of Mahuang Xixin Fuzi Tang in treating sick sinus syndrome based on network pharmacology and molecular docking

作　　者：张士彬 范妞 谢海波 ZHANG Shibin;FAN Niu;XIE Haibo(Graduate School,Hunan University of Chinese Medicine,Hunan,Changsha 410208,China;Academic Affairs Office,Hunan University of Chinese Medicine,Hunan,Changsha 410208,China)

机构地区：[1]湖南中医药大学研究生院,湖南长沙410208 [2]湖南中医药大学教务处,湖南长沙410208

出　　处：《中国医药科学》2024年第4期145-149,共5页China Medicine And Pharmacy

基　　金：全国中医临床特色技术传承骨干人才培训项目(国中医药人教函〔2019〕36号);湖南省自然科学基金面上项目(2020JJ4480)。

摘　　要：目的借助网络药理学方法探讨麻黄细辛附子汤(MXFT)治疗病态窦房结综合征(SSS)的分子机制。方法基于中药系统药理分析平台(TCMSP)检索筛选MXFT的药物活性成分,Uniport数据库查找各成分潜在靶点。OMIM、GeneCards和DisGeNET数据库查找并去重得到SSS靶点;运用String结合Cytoscape 3.9.1对交集靶点进行蛋白质相互作用分析,Metascape数据库对其进行基因本体(GO)分析及京都基因与基因组百科全书(KEGG)富集分析。通过Degree值筛选前3位的药物活性成分与前2位的基因进行分子对接。结果从MXFT中筛选有效活性成分39种,共242个靶点。从SSS中筛选靶点1376个,交集靶点242个,蛋白激酶(AKT1)、肿瘤抑制因子(TP53)等可能是治疗SSS的关键靶点。GO分析共获得453个条目,其中生物过程220个条目、细胞组分113个条目、分子功能120个条目。KEGG分析共获得222个条目,主要涉及癌症通路、脂质和动脉粥样硬化、PI3K-AKT信号通路等。结论通过网络药理学初步发现MXFT主要通过AKT1、TP53等靶点,山柰酚(kaempferol)、槲皮素(quercetin)等活性成分,通过减少心肌细胞损伤、调节离子通道等方式治疗SSS。Objective To explore the molecular mechanism of Mahuang Xixin Fuzi Tang(MXFT)in the treatment of sick sinus syndrome(SSS)using network pharmacology methods.Methods Based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),the active ingredients of MXFT were retrieved and screened,and potential targets of each ingredient were searched in the Uniport database.The OMIM,GeneCards,and DisGeNET databases were searched and deduplicated to obtain SSS targets;The String was used combined with Cytoscape 3.9.1 for protein interaction analysis of intersection targets.Metascape database was used for gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis on them.Molecular docking between the top three active ingredients of the drug and the top two genes was performed through Degree value screening.Results 39 effective active ingredients were screened from MXFT,with a total of 242 targets.1376 targets and 242 intersection targets were screened from SSS.The protein kinase(AKT1)and tumor-inhibiting factor(TP53),etc.may be key targets for the treatment of SSS.A total of 453 entries were obtained through GO analysis,including 220 entries for biological processes,113 entries for cellular components,and 120 entries for molecular functions.A total of 222 entries were obtained through KEGG analysis,mainly involving cancer pathways,lipid,and atherosclerosis,PI3K-AKT signaling pathways,etc.Conclusion Through network pharmacology,it has been preliminarily found that MXFT mainly treats SSS through targets such as AKT1 and TP53,and active ingredients such as kaempferol and quercetin,and by reducing myocardial cell damage and regulating ion channels.

关 键 词：麻黄细辛附子汤 病态窦房结综合征 网络药理学 分子对接 

分 类 号：R259[医药卫生—中西医结合] R541.7[医药卫生—中医内科学]