基于数据挖掘、网络药理学技术探讨藏药治疗慢性萎缩性胃炎的用药规律及作用机制

Analysis on Medication Regularity and Action Mechanism of Tibetan Medicine in Treatment of Chronic Atrophic Gastritis Based on Data Mining and Net-Work Pharmacology

目的研究藏药治疗慢性萎缩性胃炎(chronic atrophic gastritis,CAG)的作用机制。方法在中国知网、万方数据库、维普期刊数据库检索藏药治疗CAG的藏药复方。对符合纳入排除条件的文献进行信息提取,构建数据库统计高频词藏药,进行关联度分析,获取藏药治疗CAG的核心药物。在TCMSP数据库检索藏药活性成分及作用靶点,利用GeneCads、OMIM在线数据库获取疾病靶点,对药物作用靶点及疾病相关靶点进行韦恩分析,确定藏药治疗CAG的潜在靶点,应用String数据库、Cytoscape 3.7.1软件构建“藏药-活性成分-潜在靶点”相互作用网络与蛋白相互作用(PPI)图。使用DAVID数据库对关键靶点进行GO功能和KEGG通路富集分析。结果共纳入藏药复方78个,包含136味藏药。根据置信度与关联性选取诃子、豆蔻、荜茇、石榴子四味核心药物,筛选出槲皮素、木犀草素、玫瑰树碱、鞣花酸、胡椒碱、去氢二异丁香酚等32个药物活性成分,核心靶点为AKT1、TNF、IL6、TP53、MMP9、HIF1A、CASP3、BCL2、IL1B、PTGS2等92个,获得747条GO条目,KEGG富集条目涉及癌症相关通路、脂质与动脉粥样硬化、AGE-RAGE等共139条通路。结论通过数据挖掘筛选出豆蔻、荜茇、石榴子和诃子这四味藏药作为藏药治疗CAG的核心药物,并运用网络药理学方法分析得出这四味藏药可能通过下调AKT1、TNF、IL6和TP53等基因的表达抑制炎症因子的释放;并通过调控癌症相关通路、脂质与动脉粥样硬化、AGE-RAGE、流体剪切应力与动脉粥样硬化、IL-17等信号通路直接或间接参与机体抗炎、抗氧化、促进血管再生等过程发挥治疗CAG的作用。

Objective To study the mechanism of action of Tibetan medicine in the treatment of chronic atrophic gastritis(CAG).Method Retrieve Tibetan medicine prescriptions for the treatment of CAG on CNKI,Wanfang Database,and VIP Journal Database.Ex⁃tract information from literature that meets the inclusion and exclusion criteria,construct a database for high-frequency Tibetan medicine statistics,conduct correlation analysis,and obtain core drugs for Tibetan medicine treatment of CAG.Retrieve the active ingredients and targets of Tibetan medicine in the TCMSP database,use GeneCads and OMIM online databases to obtain disease targets,conduct Wayne analysis on drug action targets and disease-related targets,and determine potential targets for Tibetan medicine treatment of CAG.Use String database and Cytoscape 3.7.1 software to construct a“drug compound potential target”interaction network and protein interaction(PPI)network diagram.Conduct GO function and KEGG pathway enrichment analysis on key targets using the DAVID database.Results A total of 78 Tibetan medicine prescriptions were included,including 136 Tibetan medicines.Based on confidence and correlation,four core drugs including Terminalia chebula,Cardamom,Piper longum,Pomegranate,and 32 active ingredients including quercetin,luteolin,rosacetin,ellagic acid,piperine,and dehydrodiisoeugenol were selected.92 core targets including AKT1,TNF,IL6,TP53,MMP9,HIF1A,CASP3,BCL2,IL1B,PTGS2,and 747 GO entries were obtained.KEGG enrichment entries involved 139 pathways,including cancer related pathways,lipid and atherosclerosis,and AGE-RAGE.Conclusion Four Tibetan medicines,including cardamom,piper longum,pomegranate,and chebula,were selected through data mining as core drugs for the treatment of CAG.Network pharmacology methods were used to analyze and conclude that these four Tibetan medicines may inhibit the release of inflammatory cytokines by down⁃regulating the expression of genes such as AKT1,TNF,IL6,and TP53.It also plays a role in the treatment of CAG by regulating cancer�related pathways,lipid and atherosclerosis,AGE-RAGE,fluid shear stress and atherosclerosis,IL-17 and other signaling pathways,which directly or indirectly participate in the anti-inflammatory,antioxidant,and vascular regeneration processes of the body.