基于网络药理学探讨养心定悸膏抗心律失常的分子机制  

Molecular mechanism of Yangxin Dingji ointment in treatment of arrhythmia:A study based on network pharmacology

作　　者：肖满 龚年春 李鹏辉 孙瑜 彭艳梅[2] 章泽恒[3] XIAO Man;GONG Nianchun;LI Penghui;SUN Yu;PENG Yanmei;ZHANG Zeheng(Hunan University of Chinese Medicine,Changsha 410208,Hunan,China;Hunan Academy of Chinese Medicine,Changsha 410006,Hunan,China;Hunan Center for Drug Evaluation and ADR Monitoring,Changsha 410013,Hunan,China)

机构地区：[1]湖南中医药大学,湖南长沙410208 [2]湖南省中医药研究院,湖南长沙410006 [3]湖南省药品审评认证与不良反应监测中心,湖南长沙410013

出　　处：《湖南中医杂志》2023年第5期154-160,共7页Hunan Journal of Traditional Chinese Medicine

基　　金：湖南省自然科学科药联合基金项目(2021JJ80048);湖南省重点领域研发计划重点研究项目(S2021GCZDYF0795);“十四五”科技创新平台中医药名医名方制剂重点研究室;湖南省芙蓉实验室中药制剂关键技术研发平台。

摘　　要：目的:基于网络药理学探讨养心定悸膏抗心律失常的分子机制。方法:检索TCMSP、BATMAN-TCM等数据库及国内外文献,筛选获得活性成分及其对应靶点;检索GeneCards、OMIM等数据库获得疾病相关靶点;采用STRING分析靶点蛋白的互作关系;利用Cytoscape 3.9.1软件构建并合并活性成分靶点及疾病靶点相互作用关系网络,通过网络拓扑分析筛选出关键基因,并对核心靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。结果:检索到139种活性成分,预测靶点780个,疾病靶点5066个,交集靶点412个,核心靶点10个,包括胰岛素(INS)、血管内皮生长因子α(VEGFA)、胱氨酸蛋白酶3(CASP3)、白蛋白(ALB)、活化蛋白-1的转录因子(JUN)等。GO功能富集分析得到对无机物的反应、神经递质受体活性、突触膜等条目。获得KEGG信号通路222条,主要包括神经活性配体-受体相互作用、神经退行性变、cGMP-PKG等。结论:本研究揭示了养心定悸膏可通过多成分、多靶点作用于神经活性配体-受体相互作用,钙、氨基酸代谢,cGMP-PKG等多通路治疗心律失常。Objective:To investigate the molecular mechanism of Yangxin Dingji ointment anti-arrhythmia based on network pharmacology.Methods:Databases including TCMSP and BATMAN-TCM and related articles in China and globally were searched to obtain active components and their corresponding targets;databases such as GeneCards and OMIM were searched to obtain disease-related targets;STRING database was used to analyze the in-teraction between target proteins.Cytoscape 3.9.1 was used to construct and combine the interaction networks of ac-tive component targets and disease targets,the network topology analysis was used to identify core genes,and gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for the core targets.Results:The above analyses obtained 139 active compo-nents,780 predictive targets,5066 disease targets,412 intersecting targets,and 10 core targets,including INS,VEG-FA,CASP3,ALB,and JUN.GO functional enrichment analysis obtained the terms such as response to inorganic substance,neurotransmitter receptor activity,and synaptic membranes.KEGG pathway enrichment analysis obtained 222 signaling pathways,mainly including neuroactive ligand-receptor interaction,neurodegeneration,and cGMP-PKG.Conclusion:This study reveals that Yangxin Dingji ointment may exert a therapeutic effect on arrhythmia through multiple components and targets by acting on various pathways such as neuroactive ligand-receptor interac-tion,calcium/amino acid metabolism,and cGMP-PKG.

关 键 词：心律失常 养心定悸膏 网络药理学 分子机制 

分 类 号：R259.417[医药卫生—中西医结合]