基于网络药理学的健脾通络解毒方治疗慢性萎缩性胃炎作用机制研究

Mechanism of Jianpi Tongluo Jiedu Recipe in the Treatment of Chronic Atrophic Gastritis Based on Network Pharmacology

目的:基于网络药理学方法,研究健脾通络解毒方治疗慢性萎缩性胃炎(CAG)的作用机制。方法:通过中药系统药理学数据库与分析平台和UniProt数据库,获得健脾通络解毒方活性成分及靶点;检索GeneCards、OMIM和DrugBank数据库获取CAG靶点;将二者取交集,获得药物疾病共同作用靶点;之后导入STRING数据库,通过Cytoscape 3.7.2软件构建蛋白质-蛋白质相互作用网络和药物-活性成分-作用靶点-疾病网络图;进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析;再运用AutoDock Vina软件进行分子对接。结果:获得健脾通络解毒方有效成分206个,靶点232个,CAG靶点783个,共同作用靶点91个,关键靶点涉及肿瘤蛋白p53(TP53)、蛋白激酶B1(Akt1)、Jun原癌基因(JUN)、白细胞介素(IL)6、血管内皮生长因子A、肿瘤坏死因子、信号传导与转录激活因子3、前列腺素内过氧化物合酶2、胱天蛋白酶3、IL-1β、缺氧诱导因子-1和表皮生长因子等。GO功能富集分析结果表明,生物过程2 024个,细胞组成34个,分子功能120个。通过KEGG分析得到161条信号通路。分子对接结果显示结合力良好。结论:健脾通络解毒方主要通过TP53、Akt1、JUN和IL-6等蛋白,磷脂酰肌醇3激酶-Akt、丝裂原激活的蛋白激酶、肿瘤蛋白53和Janus酪氨酸蛋白激酶-信号转导与转录激活因子等信号通路对CAG发挥作用。

OBJECTIVE:To study the mechanism of Jianpi Tongluo Jiedu recipe in the treatment of chronic atrophic gastritis(CAG)based on network pharmacology.METHODS:Active components and targets of Jianpi Tongluo Jiedu recipe were obtained by traditional Chinese medicine systems pharmacology database and analysis platform and UniProt database.GeneCards,OMIM and DrugBank were searched for CAG targets.The target of drug and disease interaction was obtained by intersection of the two.After that,STRING database was imported to construct protein-protein interaction network and drug-active ingredient target-disease network map by Cytoscape 3.7.2 software.Gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed.AutoDock Vina software was used for molecular docking.RESULTS:A total of 206 effective components,232 targets,783 CAG targets and 91 co-action targets of Jianpi Tongluo Jiedu recipe were obtained.The key targets involved tumor protein p53(TP53),protein kinase B1(Akt1),Jun proto-oncogene(JUN),interleukin(IL)6,vascular endothelial growth factor A,tumor necrosis factor,signaling and transcriptional activator 3,prostaglandin peroxidase synthase 2,caspase 3,IL-1β,HIF1A and epI Skin growth factor.GO function enrichment analysis showed that there were 2024 biological processes,34 cell components and 120 molecular functions.By KEGG analysis,161 signal pathways were obtained.Molecular docking results showed good binding force.CONCLUSIONS:Jianpi Tongluo Jiedu recipe can affect CAG mainly through TP53,Akt1,JUN,IL-6 and other proteins,PI3K/Akt,MAPK,p53,JAK/STAT and other signaling pathways.