基于网络药理学探讨血府逐瘀丸治疗动脉粥样硬化的作用机制研究

Study on Action Mechanism of Xuefu Zhuyu Pill(血府逐瘀丸)in Treatment of Atherosclerosis Based on Network Pharmacology

目的通过网络药理学分析探讨中医血府逐瘀丸治疗动脉粥样硬化可能作用机制。方法运用TCMSP在线数据库获取血府逐瘀丸活性成分和靶标并经Uniprot在线数据库转换为基因名称,通过GeneCard和OMIM在线数据库收集动脉粥样硬化靶标基因。经Venn工具获取药物-疾病交集基因,后于STRING在线数据库构建蛋白相互作用网络,并利用Cytoscape 3.2.1软件获得可视化结果。运用DAVID在线数据库进行GO和KEGG通路富集分析。结果最终获得3812个疾病基因,药物活性成分151个、靶标基因94个及药物-疾病交集基因78个。GO富集分析认为血府逐瘀丸可能通过作用于泛素样蛋白连接酶结合、酰胺结合、类固醇结合、核激素受体结合、血红素结合、Hsp90蛋白结合、凋亡、雌激素受体结合等过程,影响DNA结合转录激活剂活性,RNA聚合酶Ⅱ特异性、核受体活性、直接配体调节序列特异性、DNA结合的转录因子活性、类固醇激素受体活性从而发挥治疗动脉粥样硬化的作用。涉及的通路主要包括:凋亡信号通路、AGE-RAGE信号通路、TNF信号通路、IL-17信号通路、内分泌抵抗信号通路、甲状腺激素信号通路。结论血府逐瘀丸治疗动脉粥样硬化具有多靶点、多通路的特点,可以通过多种途径实现对动脉粥样硬化发生发展过程的调控,为进一步开展血府逐瘀丸治疗动脉粥样硬化作用机制实验研究提供新的思路和可靠的依据。

Objective To explore the possible mechanism of traditional Chinese medicine Xuefu Zhuyu Pill(血府逐瘀丸)treating atherosclerosis by network pharmacology analysis.Methods The active ingredients and targets of Xuefu Zhuyu Pill were obtained by the TCMSP online database and converted into gene names through the Uniprot online database.Target genes for atherosclerosis were collected through GeneCard and OMIM online databases.The drug-disease crossover genes were obtained through the Venn tool,and then a protein-protein interaction network was constructed in the STRING online database.Cytoscape 3.2.1 software was used to obtain visual effects.GO analysis and KEGG pathway enrichment analysis were performed by using DAVID online database.Results There were 3812 disease genes,151 active components,94 target genes and 78 drug-disease intersection genes.GO enrichment analysis suggested that Xuefu Zhuyu Pill might affect DNA-binding transcription activator activity,RNA polymeraseⅡ-specific,nuclear receptor activity,transcription factor activity,direct ligand regulated sequence-specific DNA binding,steroid hormone receptor activity in the treatment of depression by acting on ubiquitin protein ligase binding,amide binding,steroid binding,nuclear hormone receptor binding,heme binding,Hsp90 protein binding,Apoptosis,Estrogen receptor binding,Glutathione binding and so on.The access involved mainly included Apoptosis signaling pathway,AGE-RAGE signaling pathway,TNF signaling pathway,IL-17 signaling pathway,Endocrine resistance signaling pathway and Thyroid hormone signaling pathway.Conclusion Xuefu Zhuyu Pill has the characteristics of multi-target and multi-pathway in the treatment of atherosclerosis,and it can regulate the development of atherosclerosis through a variety of ways,providing new ideas and reliable basis for further experimental research on the mechanism of Xuefu Zhuyu Pill in the treatment of atherosclerosis.