基于网络药理学和分子对接研究参松养心胶囊治疗心房颤动的作用机制

目的：采用网络药理学和分子对接技术研究参松养心胶囊治疗心房颤动（AF）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）和中医药百科全书数据库（ETCM）检索参松养心胶囊的活性成分及作用靶点；利用人类基因数据库（GeneCards）、治疗性靶点数据库（TTD）、在线人类孟德尔遗传（OMIM）、遗传药理学和药物基因组学数据库（PhramGKB）、疾病相关基因数据库（DISGeNET）、综合性药物数据库（DrugBank）检索得到AF疾病靶点；使用R软件绘制药物活性成分-疾病靶点韦恩图得到参松养心胶囊治疗AF的潜在靶点；利用R语言对潜在靶点进行基因本体（GO）富集分析和京都基因和基因组百科全书（KEGG）富集分析；通过Cytoscape软件构建药物活性成分-疾病靶点网络图，通过筛选得到关键靶点及药物活性成分，运用AutoDock Vina软件进行分子对接；运用PyMOL软件对分子对接结果进行可视化。结果：得到参松养心胶囊的活性成分190个、其对应靶点262个，同时检索得到3 577个与AF疾病相关靶点，二者交集靶点171个，共涉及GO功能2 549个，KEGG信号通路183条；蛋白质-蛋白质相互作用网络（PPI）最终筛选出关键靶蛋白MAPK1、MAPK8、MAPK14、JUN、STAT、FOS、TNF，将其与反向筛选的10个药物活性成分一一进行分子对接，其中有39对成分-靶点对接活性较高。其中隐丹参酮、木犀草素、山柰酚与MAPK1对接结果最佳。本研究表明参松养心胶囊是通过多成分、多靶点、多通路对AF起到治疗作用，同时笔者发现参松养心胶囊主要通过MAPK1影响心房电结构重构、调节代谢、抑制炎症反应、调节细胞凋亡等途径治疗AF。

Mechanism of Shensong Yangxin Capsules in the Treatment of Atrial Fibrillation Based on Network Pharmacology and Molecular Docking

To study the mechanism of Shensong Yangxin Capsules in the treatment of atrial fibrillation by network pharmacology and molecular docking.Methods:The active components and action targets of Shensong Yangxin Capsules were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Encyclopedia of Traditional Chinese Medicine(ETCM).The targets of atrial fibrillation were retrieved from GeneCards,TTD,OMIM,PhramGKB,DISGeNET,and DrugBank.R software was used to draw the Venn diagram of drug-active component-disease target network to obtain the potential targets of Shensong Yangxin Capsules in the treatment of atrial fibrillation.GO and KEGG enrichment analyses of potential targets were carried out by R language.The drug-active component-disease target network was plotted by the Cytoscape software,and the key targets and drug active components were obtained by screening.The molecular docking was carried out by AutoDock Vina software.PyMOL software was used to visualize the molecular docking results.Results:A total of 190 active components and 262 corresponding targets of Shensong Yangxin Capsules were obtained.A total of 3 577 targets related to atrial fibrillation were retrieved.There were 171 intersection targets,involving 2 549 GO functions and 183 KEGG signaling pathways.Key target proteins MAPK1,MAPK8,MAPK14,JUN,STAT,FOS,and TNF were finally screened out based on the protein-protein interaction(PPI) network and docked to 10 drug active components one by one,of which 39 pairs showed high docking affinity.The docking results of cryptotanshinone,luteolin,and kaempferol to MAPK1 were the best.Conclusion:Shensong Yangxin Capsules can treat atrial fibrillation through multiple components,targets,and pathways.Furthermore,the therapeutic effect of Shensong Yangxin Capsules against atrial fibrillation is achieved mainly through affecting atrial electrical structure remodeling by MAPK1,regulating metabolism,inhibiting inflammatory response,and regulating cell apoptosis.