目的:基于网络药理学探讨养心定悸胶囊治疗室性心律失常(Ventricular Arrythmia,VA)的作用机制.方法:使用中药系统药理学数据库与分析平台(TCMSP)和BATMAN-TCM等数据库筛选养心定悸胶囊的有效成分及其作用靶点,通过GeneCards、OMIM等数据库检索VA的疾病靶点,制作韦恩图,获得相关交集.使用STRING数据库制作靶点间相互作用网络,筛选关键靶点及关键成分,使用Cytoscape 3.9.1软件构建成分-靶点-通路网络.运用DAVID网站进行基因本体论(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:检索到活性成分146种,预测靶点761个,疾病靶点2 126个,交集靶点222个.构建的网络最终获得47个节点和708条边,获得10个核心靶点,包括重组人信号转导与转录激活因子3(Signal Transducer and Activator of Transcription 3,STAT3)、丝氨酸/苏氨酸蛋白激酶 1(Serine-Threonine Protein Kinase 1,AKT1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等.GO和KEGG富集分析与筛选显示,养心定悸胶囊治疗VA的作用通路包括磷代谢过程的正调控、细胞运动的正调控、对外源性刺激的反应等.结论:养心定悸胶囊治疗VA通过多成分、多靶点作用于磷代谢过程的正调控、对激素的反应、细胞运动的正调控等多通路发挥药效.
A study on the mechanism of treating ventricular arrhythmia with the Yangxin Dingji capsules based on network pharmacology
Objective:To explore the mechanism of the Yangxin Dingji capsules(养心定悸胶囊)in the treatment of ventricular arrhythmia(VA)based on network pharmacology.Methods:TCMSP and BATMAN-TCM databases were used to screen the active ingredients and target proteins of the Yangxin Dingji capsules.Disease target proteins of VA were retrieved from databases such as GeneCards and OMIM.Venn diagram was used to obtain the intersection.The protein-protein interaction network was constructed using the STRING database.Key targets and key ingredients were selected.The component-target-pathway network was constructed using Cytoscape 3.9.1 software,and Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed using the DAVID website.Results:A total of 146 active ingredients and 761 predicted target proteins of the Yangxin Dingji capsules were obtained,along with 2 126 disease target proteins of VA.The intersection yielded 222 target proteins.The constructed network was consisted of 47 nodes and 708 edges.Ten core target proteins were identified,including signal transducer and activator of transcription 3(STAT3),protein kinase B alpha(AKT1),and tumor necrosis factor(TNF).GO and KEGG mrichment analyses showed that the Yangxin Dingji capsules might exert therapeutic effects on VA through multiple components and targets,involving multiple pathways such as positive regulation of phosphorus metabolic processes,positive regulation of cell motility,response to exogenous stimuli.Conclusion:The Yangxin Dingji capsules may exert its therapeutic effects on VA by multiple components and targets,through multiple pathways such as positive regulation of phosphorus metabolic processes,response to hormones,and positive regulation of cell motility.
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