基于网络药理学分析当归-白芍药对治疗腰椎间盘退变的潜在靶点及机制

The analysis of potential targets and mechanism of Danggui-Baishao herb pair for the treatment of lumbar disc degeneration based on network pharmacology

目的探讨当归-白芍药对治疗腰椎间盘退变的作用靶点及机制方法通过中药系统药理学数据库与分析平台(TCMSP)检索、筛选当归-白芍的活性成分和作用靶点。在OMIM、Disgenet、Genecards数据库检索腰椎间盘退变的相关基因,通过R软件与当归-白芍的作用靶点相交叠,筛选当归-白芍治疗腰椎间盘退变的关键靶点。分别利用Cytoscape软件、STRING数据库构建药物-成分-靶点-疾病网络和关键靶点蛋白相互作用网络最后利用R软件进行关键靶点基因GO功能富集分析与KEEG通路富集分析结果共筛选出当归-白芍药对的14个活性成分及对应的342个关键靶点,共筛选出1110个腰椎间盘退变疾病靶点,获得药物-疾病共同靶点69个。建立的靶点蛋白相互作用网络包含69个节点、643条边,其中的关键免点蛋白AKT1、EGFR、VEGFA、CASP3、CXCL8、MAPK8、CCND1、JUN、FGF2、MAPK14 GO功能富集分析与KEGG通路富集分析显示,当归-白芍治疗腰椎间退变关键靶点基因的生物学过程和功能主要集中在内肽酶活力、金属内肽酶活性、1-磷脂酰肌醇-3-激酶活性、磷脂酰肌醇3-激酶活性、磷脂酰肌醇磷酸激酶活性、金属肽酶活性等。相关的信号通路主要包括TNF信号通路、IL-17信号通路、HIF-1信号通路、雌激素信号通路等结论当归-白芍药对通过多途径、多把点发挥治疗腰椎间盘退变的作用。

Objective To explore the targets and mechanism of Danggui-Baishao herb pair for the treatment of lumbar disc degeneration based on network pharmacology approach.Methods Through the Traditional Chinese Medicine Systems Phamiacology Database and Analysis Platform(TCMSP)to search and screen the active ingredients and targets of the Danggui-Baishao herb pair.The genes related to lumbar disc degeneration were searched in the databases of OMIM,Disgenet,and Genecards,and the target points of the Danggui-Baishao herb pair were overlapped through the R software to screen the key targets of Danggui-Baishao herb pair for the treatment of lumbar disc degeneration.Cytoscape software and STRING database were used to construct drug-component-target-disease network and key target protein interaction network.Finally,use R software to carry out the key target gene GO flinction enrichment analysis and KEEG pathway enrichment analysis.Results A total of 14 active ingredients and corresponding 342 key targets of the Danggui-Baishao herb pair were screened.A total of 1,110 targets for lumbar disc degeneration were screened,and 69 common drug-disease targets were obtained.The established target protein interaction network contained 69 nodes and 643 edges,among which the key target proteins are AKT1,EGFR,VEGFA,CASP3,CXCL8,MAPK8,CCND1,JUN,FGF2,MAPK14.GO flinction enrichment analysis and KEGG pathway enrichment analysis showed that the key target genes biological processes and flinctions of Danggui-Baishao herb pair for the treatment of lumbar disc degeneration mainly focused on endopepridase activity,metal endopeptidase activity,1-phospholipid Inositol-3-kinase activity,phosphatidylinositol 3-kinase activity,phosphatidylinositol phosphate kinase activity,metalopepddase activity,etc.The related signal pathways mainly include TNF signal pathway,IL-17 signal pathway,HIF-1 signal pathway,estrogen signal pathway and so on.Conclusion Danggui-Baishao herb pair can treat lumbar disc degeneration through multiple channels and multiple targets.