叶嘉豪 胡志希 钟森杰 杨梦 姚涛 邱宏 熊霞军

摘要 目的：分析血府逐瘀湯治疗冠心病的作用机制。方法：借助中药系统药理学数据库与分析平台（TCMSP）检索血府逐瘀汤的化学成分和靶基因，利用GeneCards获得与冠心病相关的靶基因，采用Cytoscape 3.7.2绘制“中药成分-疾病靶基因”网络图，采用String数据库构建蛋白质-蛋白质相互作用（PPI）网络图，将PPI网络图导入Cytoscape 3.7.2，借助CytoNCA插件进行网络拓扑分析，采用R64 3.6.1软件对靶基因进行GO功能和KEGG通路富集分析。结果：筛选出血府逐瘀汤相关化合物224个，作用于冠心病的相关靶点3 564个，PPI网络显示Degree值排名前10位的靶基因依次为IL6、AKT1、ALB、VEGFA、CCL2、EGF、IL1B、MMP-9、CASP3、MAPK1，拓扑分析结果显示Degree值排名前10位的靶基因依次为PTGS2、MMP2、VEGFA、AKT1、ALB、CASP3、STAT3、IL6、MMP9、SERPINE1。GO富集分析预测出此方对冠心病的治疗机制可能与调控营养水平反应、对氧含量的反应、膜筏、膜微域、磷酸酶结合等通路相关。KEGG富集分析预测出此方治疗冠心病可能是通过糖尿病并发症AGE-RAGE信号通路、流体剪切应力和动脉粥样硬化、HIF-1信号通路、TNF信号通路等几个关键的通路达到治疗效果。结论：本研究探讨了血府逐瘀汤治疗冠心病的活性成分及其作用机制，血府逐瘀汤可通过多靶点、多通路治疗冠心病，为进一步研究该方作用机制提供了理论依据。

关键词 冠心病;血府逐瘀汤;网络药理学;靶基因;通路;作用机制

Abstract Objective：To analyze the mechanism of Xuefu Zhuyu Decoction in the treatment of coronary heart disease.Methods：GeneCards was used to obtain target genes related to coronary heart disease，Cytoscape 3.7.2 was used to draw a network diagram of “Chinese medicine components-disease target genes”，String database was used to construct a PPI network diagram，the PPI network diagram was imported into Cytoscape 3.7.2，and CytoNCA plug-in was used for network topology analysis.R64 3.6.1 was used software for GO function and KEGG pathway enrichment analysis of target genes.Results：A total of 224 related compounds of Xuefu Zhuyu Decoction were screened，and 3 564 related targets for coronary heart disease were screened.The PPI network showed that the top 10 target genes with degree value were IL6，AKT1，ALB，VEGFA，CCL2，EGF，IL1B，MMP-9，CASP3，MAPK1，topological analysis results showed that the top 10 target genes with degree value were PTGS2，MMP2，VEGFA，AKT1，ALB，CASP3，STAT3，IL6，MMP9，SERPINE1.GO enrichment analysis predicted that the treatment mechanism of this formula for coronary heart disease may be related to the regulation of nutritional level response，response to oxygen content，membrane rafts，membrane microdomains，phosphatase binding and other pathways.KEGG enrichment analysis predicted that the treatment of coronary heart disease by this prescription may achieve the curatie effects through several key pathways such as the AGE-RAGE signaling pathway，fluid shear stress and atherosclerosis，HIF-1 signaling pathway，and TNF signaling pathway.effect.Conclusion：This study explores the active components of Xuefu Zhuyu Decoction on coronary heart disease and its mechanism of action.Xuefu Zhuyu Decoction treats coronary heart disease through multiple targets and multiple pathways，which provides a theoretical basis for further research on the mechanism of action of the prescription.

Keywords Coronary heart disease; Xuefu Zhuyu Decotion; Network pharmacology; Target genes; Pathways; Mechanism

中图分类号：R289.5;R541文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.09.009

冠心病是由于冠状动脉粥样硬化病变[1]，导致血管狹窄或阻塞而引起心肌组织缺血、坏死。中医将其归类为“胸痹”“真心痛”等范畴，是以膻中或左胸部发作性憋闷、疼痛为主要临床表现的一种病证。……