双心方治疗心肌梗死后抑郁的网络药理学研究

A Network Pharmacological Study of Shuangxin Prescription in the Treatment of Depression after Myocardial Infarction

目的:基于网络药理学探讨双心方治疗心肌梗死后抑郁的作用机制。方法:通过中药系统药理学数据库及分析平台(traditional Chinese medicine systems pharmacology database and analysis platform, TCMSP)获取双心方活性成分及其对应靶点,GeneCards、PharmGKB数据库搜集心肌梗死与抑郁的相关靶点并整合,将药物靶点与疾病靶点取交集后得到双心方的潜在作用靶点。使用Cytoscape 3.8.2软件构建药物—成分—潜在作用靶点网络,利用STRING数据库进行蛋白质相互作用(protein-protein interaction, PPI)网络分析,并利用DAVID V6.8数据库进行基因本体论(gene ontology, GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes, KEGG)富集分析。结果:获得双心方的有效成分88个,潜在作用靶点89个,核心靶点10个。通过GO和KEGG富集分析分别获得229条生物学过程条目和34条信号通路。通过HIF-1、PI3K/Akt等多条信号通路介导,双心方中的多重活性成分有心脏保护作用,可通过抗心肌细胞凋亡、抗炎、抗氧化应激反应,促进心肌梗死后心脏内的血管生成等治疗心肌梗死及改善预后,通过抑制神经元的氧化应激损伤、减少炎症介导的细胞毒性和神经元死亡等改善抑郁。结论:双心方主要是通过多靶点、多通路来发挥治疗心肌梗死后抑郁的作用,该研究为后续深入开展双心方治疗心肌梗死后抑郁的作用机制研究提供了依据与方向。

Objective: To explore the action mechanism of Shuangxin Prescription in the Treatment of Depression after Myocardial Infarction based on network pharmacology.Methods: The active components and their corresponding targets of Shuangxin Prescription were obtained through the raditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),the related targets of myocardial infarction and depression were collected and integrated in GeneCards and PharmGKB databases, and the potential target of Shuangxin Prescription was obtained after the intersection of drug target and disease target.The drug component potential target network was constructed using Cytoscape 3.8.2,the protein-protein interaction(PPI) network was analyzed using STRING database, and the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) were enriched and analyzed using DAVID V6.8 database.Results: 88 active components, 89 potential targets and 10 core targets were obtained.229 biological process entries and 34 signal pathways were obtained by GO and KEGG enrichment analysis, respectively.The multiple active components in Shuangxin Prescription had cardioprotective effects mediated by multiple signal pathways such as HIF-1 and PI3 K/Akt.It could treat myocardial infarction and improve prognosis by anti-cardiomyocyte apoptosis, anti-inflammatory and anti-oxidant stress response, promote angiogenesis in the heart after infarction, and improve depression by inhibiting neuronal oxidative stress injury, reducing inflammation mediated cytotoxicity and neuronal death.Conclusion: Shuangxin Prescription mainly plays a role in the treatment of depression after myocardial infarction through multi-target and multi-channel.This study provides a basis and direction for the follow-up in-depth study of the mechanism of Shuangxin Prescription in the treatment of depression after myocardial infarction.