基于“胃脘痈”与“炎-癌链”理论治疗慢性萎缩性胃炎的机制分析

Treatment of chronic atrophic gastritis based on theories of"gastric carbuncle"and"inflammation-cancer axis":A mechanistic study

目的探讨黄连-蒲公英药对治疗慢性萎缩性胃炎阻断“炎-癌链”的可能机制。方法通过中药系统药理学技术平台(TCMSP)、BATMAN-TCM数据库获取黄连-蒲公英药对的主要活性成分,并用Uniprot数据库矫正靶点,利用人类基因数据库(Gene Cards)筛选慢性萎缩性胃炎的疾病靶点,采用Venny 2.1软件将药物靶点和疾病靶点取交集,获得黄连-蒲公英治疗慢性萎缩性胃炎的作用靶点。采用String数据库和Cytoscape 3.8.2软件绘制蛋白相互作用网络(PPI),使用DAVID 6.8数据库进行潜在基因的基因本体(GO)分析和基因组百科全书(KEGG)通路富集分析,并绘制中药-成分-靶点-通路图。结果最终得到黄连-蒲公英药对有效成分17个,交集基因63个,最主要的有效成分为槲皮素、巴马汀、七叶亭、黄连素等,PPI网络图中度值较高的靶点有白细胞介素6(IL-6)、肿瘤坏死因子(TNF)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、细胞肿瘤抗原53(TP53)、血管内皮生长因子A(VEGFA)、白细胞介素8(CXCL8)、转录因子AP-1(JUN)、前列腺素G/H合酶2(PTGS2)、Caspase3、丝裂原活化蛋白激酶(MAPK1)、基质金属蛋白酶(MMP)-9、IL-10。GO富集分析共430个生物学过程;KEGG通路图中与慢性萎缩性胃炎密切相关的有:癌症的途径、TNF信号通路、缺氧诱导因子-1(HIF-1)信号通路、细胞凋亡、癌症中的蛋白多糖、核转录因子(NF)-κB信号通路。结论基于“胃脘痈”理论的黄连-蒲公英药对治疗慢性萎缩性胃炎是通过多成分、多靶点、多通路共同阻断“炎-癌链”的进程。

Objective To investigate the possible mechanism underlying the actions of the rhizoma cop-tidis-dandelion herb pair in blocking the inflammation-cancer axis as a treatment of chronic atrophic gastritis.Methods The major active ingredients of the rhizoma coptidis-dandelion herb pair were obtained via TCMSP and BATMAN-TCM databases.UniProt database was used to query the human gene corresponding to each target pro-tein.The human gene database Gene Cards was used to screen the gene targets of chronic atrophic gastritis.Ven-ny 2.1 software was used to obtain the intersection of drug targets and disease targets,such that the action targets of rhizoma coptidis-dandelion herb pair in the treatment of chronic atrophic gastritis were determined.String database and Cytoscape 3.8.2 software were used to generate a protein-protein interaction network(PPI).Using DAVID 6.8 database,gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)en-richment analysis of the potential genes were performed.A network diagram of Chinese herbal medicine-compo-nent-target was mapped.Results Finally,17 active ingredients and 63 intersection genes were identified in the rhizoma coptidis-dandelion herb pair.The most important active ingredients included quercetin,palmatine,es-culetin and berberine.The targets with higher PPI values in the PPI network included IL-6,TNF,AKT1,TP53,VEGFA,CXCL8,JUN,PTGS2,CASP3,MAPK-1,MMP-9,and IL-10.GO enrichment analysis revealed a total of 430 biological processes.In KEGG analysis,pathways closely related to chronic atrophic gastritis included the cancer pathway,TNF signaling pathway,HIF-1 signaling pathway,apoptosis,proteoglycan in cancer,and NF-κB signaling pathway.Conclusion Treatment of chronic atrophic gastritis with Rhizoma coptidis-dandelion herb pair based on the"gastric carbuncle"theory works by blocking the"inflammation-cancer axis"via combined actions of a multi-component,multi-target,and multi-pathway process.