附子理中汤治疗腹泻型肠易激综合征的网络药理学机制研究

Study on Mechanism of Fuzi Lizhong Decoction(附子理中汤)in Treatment of Diarrhea Predominant Irritable Bowel Syndrome Based on Network Pharmacology Method

目的通过网络药理学方法探讨附子理中汤治疗腹泻型肠易激综合征(IBS-D)的潜在分子生物学机制。方法通过TCMSP数据库筛选附子理中汤所有药物的有效成分、作用靶点,运用GeneCards、OMIM数据库筛选与IBS-D有关的疾病靶点,并借助Cytoscape 3.7.2构建"药物—成分—靶点—疾病"可视化网络,利用STRING平台构建药物-疾病靶点交互网络,利用DAVID数据库对关键靶点蛋白进行GO基因本体富集分析及KEGG通路富集分析。结果根据筛选条件[口服生物利用度(OB)≥30%、类药性(DL)≥0.18]共得到114个活性成分,167个药物潜在靶点。2个疾病数据库以"Diarrhea Predominant Irritable Bowel Syndrome"为搜索条件共收集到2279个疾病靶点,药物-疾病共同靶点104个。根据PPI网络筛选出附子理中汤干预IBS-D的核心靶标蛋白91个,主要涉及JUN、MAPK3、MAPK1、TNF、AKT1、STAT3、RELA、MAPK14、NR3C1等。根据错误发现率(FDR)<0.05,确定GO基因功能12个条目。KEGG富集分析得到65条通路,主要涉及TNF信号通路、Toll样受体信号通路、NOD样受体信号通路等。结论附子理中汤治疗IBS-D是多成分、多靶点、多途径相互作用的结果,为附子理中汤的临床应用以及IBS-D相关疾病的基础或临床研究提供一定的理论依据。

Objective To explore the potential molecular mechanism of Fuzi Lizhong Decoction(附子理中汤)in the treatment of diarrhea predominant irritable bowel syndrome(IBS-D)through pharmacology network.Methods TCMSP database was adopted to screen the active components and effect targets of all herbal ingredients in Fuzi Lizhong Decoction.Genecards and OMIM databases were used to collect disease targets for IBS-D.Cytoscape3.7.2 software was used to construct the drug-component-targetdisease network diagram.The STRING platform was used to construct the drug-disease target interaction network.DAVID database was used to perform GO biological process analysis and KEGG pathway enrichment analysis of centre target proteins.Results A total of 114 active ingredients and 167 potential drug targets were obtained according to the screening conditions(OB≥30%,DL≥0.18).A total of 2279 disease targets were collected from the two disease databases under the search criteria of Diarrhea Predominant Irritable Bowel Syndrome.According to PPI network,91 centre target proteins of Fuzi Lizhong Decoction were screened,mainly involving JUN,MAPK3,MAPK1,TNF,AKT1,STAT3,RELA,MAPK14 and NR3C1.GO biological process analysis identified 12 entries based on false discovery rate(FDR)≤0.05.KEGG enrichment analysis showed 65 pathways,mainly involving in TNF signaling pathway,Toll-like receptor signaling pathway,NOD-like receptor signaling pathway and so on.Conclusion Fuzi Lizhong Decoction can treat IBS-D through multi-ingredient,multi-target and multi-pathway interaction,which provides a theoretical basis for the clinical applicationof Fuzi Lizhong Decoction and the basic or clinical research of IBS-D related diseases.