目的 基于GEO基因芯片、网络药理学及分子对接技术探讨参苓脾喜汤防治慢性胃炎(CG)、胃黏膜上皮内瘤变(GIN)、胃早期癌(EGC)的作用机制.方法 从GEO数据库下载含CG、GIN、EGC基因芯片GSE130823,使用R4.1.1筛选共同差异表达基因.利用TCMSP数据库筛选参苓脾喜汤活性成分及对应靶点,使用R4.1.1 对共同表达基因与药物靶点取交集,通过Cytoscape3.9.1软件构建中药-活性成分-靶点网络,并通过STRING数据库构建蛋白相互作用(PPI)网络并进行拓扑分析,以筛选核心靶点,使用R4.1.1对交集基因进行GO功能和KEGG通路富集分析.最后将排名靠前的药物活性成分与核心靶点蛋白进行分子对接验证.结果 共筛选出1 115个差异表达基因,参苓脾喜汤活性成分119种,靶点247个,主要活性成分包括槲皮素、豆甾醇、木犀草素等.预测得到参苓脾喜汤治疗CG、GIN、EGC潜在作用靶点22个,包括CHRM3、AR、ADRB2、DPP4等.GO功能和KEGG富集分析结果显示,参苓脾喜汤治疗CG、GIN、EGC主要涉及对cAMP、IL-17、TNF、离子跨膜转运蛋白活性的调节、钙信号通路等方面.分子对接结果显示,木犀草素与ALB、AR、DPP4有较强结合能力,槲皮素与ALB、DPP4有较强结合能力,豆甾醇与AR有较强结合能力.结论 参苓脾喜汤中多种活性成分可能通过cAMP、IL-17、TNF等信号通路,调控ALB、AR、DPP4、CYP3A4等靶点治疗CG、GIN、EGC.
Objective To explore the mechanism of Shenling Pixi Decoction in the prevention and treatment of chronic gastritis,gastric intraepithelial neoplasia and early gastric cancer based on GEO gene chip,network pharmacology and molecular docking technology.Methods A chip GSE130823 containing genes for chronic gastritis,gastric intraepithelial neoplasia and early gastric cancer was downloaded from the GEO database,and R4.1.1 was used to screen for co differentially expressed genes.The TCMSP platform was used to screen the effective chemical components and corresponding target of Shenling Pixi Decoction,and R4.1.1 was used to obtain the intersection of differentially expressed gene and drug target.Cytoscape 3.9.1 software was used to construct a Chinese materia medica-active component-target network,and protein interaction(PPI)network construction and topology analysis were performed on the STRING platform to screen core target.R4.1.1 was used to perform GO function and KEGG pathway enrichment analysis on the intersection targets.Finally,molecular docking verification was performed between the active components of the top ranked drugs and the core target protein structure.Results A total of 1 115 differentially expressed genes were obtained.119 active components and 247 target were selected from the Shenling Pixi Decoction.The main active components included quercetin,stigmasterol,luteolin,etc.22 potential targets for the treatment of CG,GIN and EGC with Shenling Pixi Decoction were obtained after prediction,including CHRM3,AR,ADRB2,DPP4,etc.The GO function and KEGG enrichment analysis results showed that the treatment of CG,GIN,and EGC with Shenling Pixi Decoction mainly involved the regulation of cAMP,IL-17,TNF,ion transmembrane transport protein activity,calcium signaling pathways,and other aspects.The molecular docking results showed that luteolin has strong binding ability with ALB,AR,and DPP4,quercetin has strong binding ability with ALB and DPP4,and stigmasterol has good docking with AR.Conclusion Multiple active components in Shenling Pixi Decoction may regulate target such as ALB,AR,DPP4 and CYP3A4 for treating CG,GIN,and EGC through signaling pathways such as cAMP,IL-17 and TNF.