摘要
目的:运用网络药理学及分子对接分析交泰丸治疗心律失常的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)与BATMAN数据库检索黄连、肉桂的活性成分和靶基因,利用GeneCards数据库检索得到与心律失常相关的靶基因,采用Cytoscape软件绘制交泰丸的“活性成分-作用靶点”网络图,采用STRING数据库构建交泰丸治疗心律失常的蛋白质-蛋白质相互作用(Protein Protein Interaction,PPI)网络图,将PPI网络图导入Cytoscape,采用DAVID数据库对药物-疾病交集靶点进行基因本体(Gene Ontology,GO)富集分析和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,使用Autodock Vina和Pymol进行分子对接。结果:共收集到交泰丸31个有效成分及其556个成分靶点;心律失常相关靶点2205个;药物成分和疾病的共有靶点174个;使用Cytoscape拓扑分析得到小檗浸碱、表小檗碱、黄藤素、黄柏酮、小檗碱等20个核心成分,PPI网络得到ALB、AKT1、MAPK3、VEGFA、SRC等15个关键核心靶点。生物信息学富集分析中共获取821个GO条目,109条KEGG通路,主要涉及PI3K-AKT信号通路、Rap1信号通路、cAMP信号通路、甲状腺激素信号通路、HIF-1信号通路等。分子对接结果表明,度值排名前5的主要活性成分与核心靶点(ALB、AKT1、MAPK3、VEGFA、SRC)有较强的亲和力。结论:该研究揭示了交泰丸可能通过调控细胞代谢、降低氧化刺激、改善血管重塑等方面治疗心律失常,为后续研究交泰丸治疗心律失常提供一定的中药药理依据。
Objective:To analyze the action mechanism of Jiaotai Pills in the treatment of arrhythmia by network pharmacology and molecular docking.Methods:The active components and their target genes of Rhizoma Coptidisn(黄连)and Cortex Cinnamomi(肉桂)were obtained through TCMSP platform and BATMAN database,GeneCards database retrieval were used to get the target genes associated with arrhythmia.Cytoscape software was used to draw“active ingredient-action target”network graph.The STRING database was used to construct protein-protein interaction(PPI)network diagram of Jiaotai Pills in the treatment of arrhythmia.PPI network diagram was imported into Cytoscape.The DAVID database was used to perform GO(Gene Ontology)function and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis on drug-disease intersection targets,and Autodock Vina and Pymol were used for molecular docking.Results:A total of 31 active components and 556 component targets of Jiaotai Pills were collected.There were 2205 targets related to arrhythmia;174 drug and disease intersection targets were obtained;The Cytoscape topological analysis was used to obtain 20 core components such as berlambin,epiberberine,palmatine,obacunone,berberine and etc.and PPI network was used to obtain 15 core targets such as ALB,AKT1,MAPK3,VEGFA,SRC.A total of 821 GO terms and 109 KEGG pathways were obtained through bioinformatics enrichment analysis,mainly involving PI3K-AKT signaling pathway,Rap1 signaling pathway,cAMP signaling pathway,thyroid hormone signaling pathway,HIF-1 signaling pathway,etc.The results of molecular docking showed that the main active components had strong affinity with the core target(ALB,AKT1,MAPK3,VEGFA,SRC).Conclusion:This study revealed the mechanism of Jiaotai Pills in the treatment of arrhythmia by regulating cellular metabolism,reducing oxidative stress,improving vascular remodeling,providing some pharmacological basis for the follow-up study on the treatment of arrhythmia by Jiaotai Pills.
作者
常燕
林建国
李成
张晓彤
汤文丽
姚魁武
CHANG Yan;LIN Jianguo;LI Cheng;ZHANG Xiaotong;TANG Wenli;YAO Kuiwu(Beijing University of Chinese Medicine,Beijing 100029,China;Guang′anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)
出处
《世界中医药》
CAS
2021年第13期1948-1953,1959,共7页
World Chinese Medicine
基金
国家自然科学基金面上项目(81873173)
首都卫生发展科研专项项目(2018-2-4153)
中医药现代化研究专项(2019YFC1708703)。
关键词
交泰丸
心律失常
网络药理学
分子对接
中药药理
作用机制
Jiaotai Pills
Arrhythmia
Network pharmacology
Molecular docking
Pharmacology of Chinese medicine
Mechanism of action
作者简介
常燕(1990.12—),女,硕士研究生在读,研究方向:中西医结合治疗心血管疾病,E-mail:771591942@qq.com;通信作者:姚魁武(1974.04—),男,博士,主任医师,博士研究生导师,研究方向:中西医结合治疗心血管疾病,E-mail:yaokuiwu@126.com。
