生脉散合真武汤加减治疗扩张型心肌病的网络药理学分析

Network Pharmacology Analysis of Modified Shengmai San and Zhenwu Decoction in Treatment of Dilated Cardiomyopathy

目的:运用网络药理学探讨生脉散合真武汤加减对扩张型心肌病(DCM)的作用机制。方法:利用中药系统药理学数据库、通用蛋白质资源数据库获得生脉散合真武汤加减的活性成分及其作用靶点;基于Cytoscape软件绘制出各中药潜在靶点间的交集靶点,筛选出生脉散合真武汤加减的活性成分;利用CytoNCA插件,构建靶点蛋白质交互作用关系网络并进行拓扑学分析;筛选出中药作用于疾病的核心靶点;在Metascape数据库中导入核心靶点分别进行GO富集分析和KEGG富集分析。结果:基于TCMSP平台和Uniprot数据库共筛选到66种活性成分和608个靶点。生脉散合真武汤加减治疗DCM的靶点蛋白交集网络共3941个节点、104319条边。共126个靶点可以作为关键靶点。Degree值最高的靶点为核仁磷酸蛋白、异质核核糖核蛋白A1、热休克蛋白家族A(Hsp70)成员5、热休克蛋白家族A(Hsp70)成员8等。GO富集分析结果共有3780个GO条目,其中2799个生物过程条目、505个细胞组分条目和476个分子功能条目,主要包括巨核细胞分化的负调控、细胞周期、有丝分裂等;KEGG富集分析结果共有94条通路,主要包括病毒致癌、沙门菌感染、剪接体、癌症中的蛋白聚糖等。结论:生脉散合真武汤加减治疗DCM主要涉及β-谷甾醇、人参皂苷rh2等活性成分,核仁磷酸蛋白、异质核核糖核蛋白A1等靶点,病毒致癌、沙门菌感染等通路。生脉散合真武汤加减可通过多成分、多靶点、多通路参与治疗DCM。

Objective:To explore the possible mechanism of modified Shengmai San and Zhenwu Decoction in treatment of dilated cardiomyopathy(DCM)by network pharmacology.Methods:The active components and their targets of modified Shengmai San and Zhenwu Decoction were obtained by TCM pharmacology database and General Protein resource database.Based on Cytoscape software,the intersection of potential targets of each Chinese medicine was plotted,and the active components of modified Shengmai San and Zhenwu Decoction were screened.CytoNCA plug-in was used to construct the target protein interaction network and carry out topology analysis.The core target of TCM on the disease was screened;Core targets were imported into Metascape database for GO enrichment analysis and KEGG enrichment analysis.Results:A total of 66 active components and 608 core targets were screened based on TCMSP platform and Uniprot database.A total of 3941 nodes and 104319 edges were found in the target protein intersection network for DCM treatment with modified Shengmai San and Zhenwu Decoction.A total of 126 targets could serve as the key targets.The targets with the highest Degree values were nucleolar phosphoprotein,heterogeneous nuclear ribonucleoprotein A1,heat shock protein family A(Hsp70)member 5,heat shock protein family A(Hsp70)member 8.There were 3780 GO items in GO enrichment analysis,including 2799 biological process items,505 cellular component items and 476 molecule function items,involving negative regulation of megakaryocyte differentiation,cell cycle,and mitosis.There were 94 pathways in KEGG enrichment analysis,including viral carcinogenesis,Salmonella infection,spliceosomes,and proteoglycans in cancer.Conclusion:The treatment of DCM with modified Shengmai San and Zhenwu Decoction mainly involves active components such asβ-sitosterol and ginsenoside rh2,targets such as nucleolar phosphoprotein and heterogeneous nuclear ribonucleoprotein A1,pathways such as viral carcinogenesis and Salmonella infection.The modified Shengmai San and Zhenwu Decoction can participate in the treatment of DCM through multiple components,multiple targets and multiple pathways.