基于网络药理学探讨丹参饮治疗胃癌前病变的作用机制

Study on the mechanism of Danshen Yin in the treatment of precancerous lesions of gastric cancer based on network pharmacology

目的:利用网络药理学分析探讨丹参饮治疗胃癌前病变的作用机制。方法:利用中药系统药理学数据库和分析平台(TCMSP)获取丹参、砂仁、檀香的活性成分及靶点,通过GeneCards数据库获取胃癌前病变疾病基因,在与丹参饮靶点映射后获得交集靶点,利用Cytoscape 3.7.1软件构建“中药-有效成分-交集靶点-疾病”网络图,并分析该网络;通过STRING数据库结合Cytoscape 3.7.1软件构建交集靶点蛋白质-蛋白质相互作用网络;将交集靶点导入至DAVID(2021 Update)数据库,进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。结果:预测获得丹参饮治疗胃癌前病变的有效活性成分76个,67个交集靶点。蛋白质-蛋白质相互作用分析得到18个核心靶点。GO功能富集分析获得369项条目,KEGG富集在90条通路上。结论:丹参饮可能通过木犀草素、丹参酮ⅡA等有效成分调节磷脂酰肌醇3激酶/蛋白激酶B信号通路、叉头框蛋白(FoxO)信号通路、缺氧诱导因子(Hypoxia Inducible Factor,HIF)-1α信号通路、肿瘤坏死因子信号通路等,发挥抗炎、调控细胞周期的作用以治疗胃癌前病变。

Objective:To explore the mechanism of Danshen Yin(丹参饮)in the treatment of precancerous lesions of gastric cancer by network pharmacological analysis.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database was used to obtain the main chemical constituents and corresponding targets of Danshen(Salvia miltiorrhiza Bunge),Sharen(Amomum villosum Lour),and Tanxiang(Santalum album linn).After mapping with Danshen Yin target,the intersection target was obtained,and Cytoscape 3.7.1 software was used to construct the network diagram of TCM medicine-active components-intersection targets-diseases and analyze the network.Through STRING database combined with Cytoscape 3.7.1 software,a target-protein interaction network(PPI)was constructed.The intersection targets were imported into David(2021 Update)database for gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses.Results:A total of 76 active components and 67 intersecting targets of Danshen Yin in the treatment of precancerous lesions of gastric cancer were predicted.The PPI analysis yielded 18 core targets.Finally 369 items were obtained by GO functional enrichment analysis,and KEGG was enriched in 90 pathways.Conclusion:Danshen Yin may regulate PI3K/Akt signal pathway,FoxO signal pathway and HIF-1αsignal pathway and TNF signal pathway through effective components such as luteolin and tanshinoneⅡA,playing the role of anti-inflammatory and regulating cell cycle in the treatmment of precancerous lesions of gastric cancer.