基于网络药理学探索真武汤治疗慢性心力衰竭作用机制研究

Research on the Mechanism of Zhenwu Decoction in Treating Chronic Heart Failure Based on Network Pharmacology

目的使用网络药理学的研究方法对真武汤治疗慢性心力衰竭的作用机制进行研究探讨。方法在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)筛选真武汤的活性化合物成分,运用Perl编程语言以及通用蛋白(Universal Protein,uniprot)数据库得到真武汤的基因靶点;在GeneCards数据库检索和筛选慢性心力衰竭相关疾病基因靶点进行检索,使用R语言筛选出共同的靶点并构建韦恩图;应用Cytoscape 3.7.1软件构建"活性成分-靶点"网络图;将共同靶点输入功能蛋白关联网络STRING数据库,获得蛋白-蛋白相互作用(protein-protein interaction,PPI)网络模型;使用R语言对"活性成分-靶点"相互作用网络图中的核心靶点基因进行基因本体论(gene ontology,GO)功能注释和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果预测得到真武汤活性化合物成分中51种以及潜在靶点381个;得到慢性心力衰竭疾病相关靶点980个,得到真武汤-慢性心力衰竭共同靶点20个,度值较高的活性成分包括β-谷甾醇(β-sitosterol)、山柰酚(kaempferol)、石防风素(deltoin)等,度值较高的靶点蛋白包括前列腺素内过氧化合物合酶(PTGS1)、核受体亚家族3组C成员2(NR3C2)、毒蕈碱型乙酰胆碱受体亚型3(CHRM3)、乙酰胆碱酯酶(ACHE)等;PPI网络中的核心基因包括白细胞介素-6(IL-6)、半胱氨酸天冬氨酸蛋白水解酶-3(CASP3)、丝裂原活化蛋白激酶-8(MAPK8)、细胞间黏附分子-1(ICAM1)、过氧化物酶体增生激活受体γ(PPARG)等;共同作用靶点主要富集于21种生物功能与61条信号通路上。结论通过运用网络药理学的研究方法我们发现真武汤治疗慢性心力衰竭具有多靶点、多通路的特点,从抑制炎症反应、调节免疫功能及调控细胞凋亡等多个机制治疗慢性心力衰竭。

Objective To investigate the mechanism of Zhenwu Decoction in the treatment of chronic heart failure(CHF)by the network pharmacology. Methods The active compounds of Zhenwu Decoction were screened on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database platform,and the gene targets of Zhenwu Decoction were obtained by using Perl language and Universal Protein(uniprot)database. GeneCards database was used to search and screen the gene targets of CHF related diseases,and R language was used to screen the common targets and construct Venn diagram. Cytoscape 3.7.1 software was used to construct the"active component-disease target"network diagram. The common targets were input into the STRING database to obtain the protein-protein interaction(PPI)network model. Gene ontology(GO)function annotation and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of core target genes in the"active componenttarget"interaction network map were conducted by using R language. Results 51 active compounds and 381 potential targets in Zhenwu Decoction were obtained,and 980 targets related to CHF were obtained. Twenty common targets for CHF were obtained. Higher degrees of active ingredients including beta sitosterol,kaempferia,deltoin,etc. The target proteins of high degree value were including Endoprostaglandin peroxidase(PTGS1),Nuclear receptor subfamily 3 group C member 2(NR3C2),muscarinic acetylcholine receptor subfamily 3(CHRM3),acetylcholinesterase(ACHE),etc. Core genes in PPI network include interleukin-6(IL-6),caspase 3(CASP3),mitogen activated kinase-8(MAPK8),intercellular cell adhesion molecule 1(ICAM1),peroxidosomal proliferation-activated receptor gamma(PPARG),etc. The co-acting targets were mainly concentrated in 21 biological functions and 61 signaling pathways. Conclusion Through the research method of network pharmacology,we found that Zhenwu Decoction has the characteristics of multi-target and multi-pathway in the treatment of CHF,and it can be used to treat chronic heart failure by inhibiting inflammatory response,regulating immune function and regulating apoptosis and so on.