网络药理学联合基因表达数据库芯片分析及分子对接技术探讨健脾清化化瘀汤治疗胃癌前病变的潜在机制

Exploring the potential mechanism of Jianpi Qinghua Huayu Decoction in the treatment of precancerous lesions of gastric cancer based on network pharmacology combined with GEO chip analysis and molecular docking technology

目的基于网络药理学联合基因表达数据库(GEO)芯片分析及分子对接技术探讨健脾清化化瘀汤治疗胃癌前病变(PLGC)的成分靶点及信号通路,预测其潜在作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP)及本草组鉴数据库(HERB)搜集健脾清化化瘀汤中14味药物的活性成分和靶点。通过GEO数据库中的GSE55696基因芯片获取差异表达基因,利用人类孟德尔遗传在线数据库(OMIM)、Dis Ge Net、Gene Cards疾病数据库获取PLGC的相关疾病靶点,运用R软件获取健脾清化化瘀汤治疗PLGC的关键靶点。通过R语言对关键靶点进行基因本体论(GO)和京都基因和基因组的百科全书(KEGG)通路富集分析,利用蛋白互作(STRING)数据库及Cytoscape3.9.1软件绘制关键靶点的蛋白质-蛋白质相互作用(PPI)网络,筛选出核心靶点,利用Cytoscape3.9.1构建健脾清化化瘀汤与PLGC的“活性成分-关键靶点”网络,筛选出核心成分,最后将核心成分与核心靶点进行分子对接,探索蛋白与分子间的亲和性。结果共获得健脾清化化瘀汤226个活性成分,对应416个药物靶点;获得PLGC差异表达基因1673个,疾病数据库获得相关靶点1302个;药物与疾病交集基因149个;GO功能富集分析得到2802个条目,KEGG通路富集分析得到161条相关通路,主要涉及糖尿病并发症晚期糖基化终末产物/AGEs受体(AGE-RAGE)信号通路与癌症相关信号通路;筛选得到核心活性成分槲皮素、木犀草素等,核心靶点TP53、JUN、AKT1等;分子对接结果证实核心成分与核心靶点之间有较好的结合活性。结论健脾清化化瘀汤可能通过参与多条信号通路作用于多成分、多靶点,从而发挥治疗PLGC的效用。

Objective To investigate the component targets and signaling pathways of Jianpi Qinghua Huanyu Formula in the treatment of gastric precancerous lesions s(PLGC)based on network pharmacology combined with gene expression database(GEO)chip analysis and molecular docking technology,and to predict its potential mechanism.Methods The TCMSP and HERB database was used to collect the effective components and targets of 14 drugs in Jianpi Qinghua Huayu Formula.Differentially expressed genes were obtained through the CSE55696 gene chip in the GEO database.Relevant disease targets of PLGC were obtained by using the DisGeNet,OMIM,and GeneCards disease databases,and the R software was used to obtain the major targets of the treatment of PLGC by Jianpi Qinghua Huayu Decoction.GO and KEGG enrichment analysis of major targets are carried out through R language,and PPI networks of major targets were plotted by STRING database and Cytoscape to screen out core targets,and"effective components-major targets"network of Jianpi Qinghua Huayu Decoction and PLGC were constructed by using Cytoscape to screen out core ingredients components,and finally connect core components with core targets to explore the affinity between proteins and molecules.Results A total of 226 effective components of Jianpi Qinghua Huayu Decoction were obtained,corresponding to 416 drug targets.1673 differentially expressed PLGC genes were obtained,and 1302 related targets were obtained in the disease database,so does 149 intersection genes for drugs and diseases.2802 items were gained by GO enrichment analysis,and 161 related pathways were obtained through KEGG pathway enrichment analysis,mainly involving AGE-RAGE signaling pathway in diabetic complications and cancer-related signaling pathways.The core effective component quercetin,luteolin,etc.were screened,so do core targets TP53,JUN,AKT1,etc..Molecular docking technology was used to confirm that there was positive binding activity between core components and core targets.Conclusion Jianpi Qinghua Huayu Formula may act on multiple components and targets by participating in multiple signal pathways,thus playing the role of treating PLGC.