麻子仁丸治疗术后肠梗阻的网络药理研究

Maziren Pills in Treatment of Postoperative Ileus by Network Pharmacology

目的:通过网络药理学预测麻子仁丸治疗术后肠梗阻(POI)作用靶点,探讨其多成分-多靶点-多通路的潜在作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)收集麻子仁丸中药化学成分,经口服生物利用度(OB)、类药性(DL)筛选得到药物的有效成分,并进行有效成分靶点预测;同时从GeneCards、OMIM、DisGeNet数据库检索POI相关靶点;取交集靶点后,使用Cytoscape 3.7.2软件构建成分-靶点互作网络;利用String数据库绘制靶点蛋白-靶点蛋白相互作用网络;并对核心靶点和核心成分分子对接;最后利用Metascape数据库进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)通路富集分析。结果:本研究共收集到POI相关靶点405个,麻子仁丸活性成分140个,涉及治疗POI靶点75个;GO生物过程分析显示,涉及对无机物的反应、对有害物质的反应、药物细胞应答、细胞因子介导的信号传导途径、对脂多糖的反应、对氧化应激的反应、对细菌源分子的反应、激酶活性的正调控、转移酶活性的正调控等。KEGG分析结果显示,涉及PI3K-AKT信号通路、TNF通路、HIF-1通路、IL-17通路、ErbB通路等信号通路。结论:麻子仁丸可通过潜在的多途径、多靶点、多通路改善术后肠梗阻炎症反应、调节肠黏膜免疫及肠道微循环等。

Objective:To predict the targets of Maziren Pills in the treatment of postoperative ileus(POI)by network pharmacology and explore its multi-component,multi-target,and multi-pathway mechanism.Methods:The chemical components of Maziren Pills were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the effective components were obtained according to oral bioavailability(OB)and drug-likeness(DL),followed by the prediction of targets of the effective components.POI-related targets were retrieved from GeneCards,OMIM,and DisGeNet.After the common targets were obtained,the component-target interaction network was constructed by Cytoscape 3.7.2.The protein-protein interaction(PPI)network was plotted by using String.The core targets were docked to core components.Metascape was used for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Results:A total of 405 POI-related targets,140 active components of Maziren Pills,and 75 therapeutic targets were obtained.As revealed by GO enrichment analysis,biological processes involved response to inorganic substance,response to hazardous substance,cellular response to the drug,cytokine-mediated signaling pathway,response to lipopolysaccharide,response to oxidative stress,response to molecule of bacterial origin,positive regulation of kinase activity,positive regulation of transferase activity,etc.As revealed by KEGG enrichment analysis,pathways involved the PI3K-AKT signaling pathway,TNF signaling pathway,HIF-1 signaling pathway,IL-17 signaling pathway,ErbB signaling pathway,etc.Conclusion:Maziren Pills can improve postoperative intestinal obstruction inflammation,regulate intestinal mucosal immunity and intestinal microcirculation through multiple potential pathways,multiple targets and multiple pathways.