基于生物信息学和网络药理学方法探讨麦门冬汤治疗特发性肺纤维化的miRNA预测及其作用机制

Exploration into miRNA Prediction of Maimendong Tang in the Treatment of Idiopathic Pulmonary Fibrosis and the Mechanism Based on Bioinformatics and Network Pharmacology

目的:通过生物信息学与网络药理学方法探求麦门冬汤治疗特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)的微小RNA和相关作用机制。方法:通过在线数据库查检麦门冬汤的有效活性成分及其相关靶基因与IPF的疾病靶点,GEO数据库下载GSE53845基因芯片,筛选GSE53845与疾病共同表达的基因。取药物和疾病交集靶点上传至miRNA在线数据库预测关键基因靶点相关微小RNA,运用DAVID数据库对关键靶基因进行GO和KEGG分析,采用iGEMDOCK进行分子对接分析,结合相关文献分析麦门冬汤防治IPF的作用机制。结果:麦门冬汤共含有502个活性化合物及1039个预测靶点;43个共同表达的IPF疾病基因靶点;关键靶点MMP3与化合物β-胡萝卜素结合性能最佳。结论:麦门冬汤主要通过miR-29家族、let-7家族、miR-26a-5p等微小RNA调节靶基因,干预IPF进程;主要作用于胶原分解过程、细胞外基质组织、细胞外基质分解等生物学过程;参与NF-κB信号通路、ECM-受体相互作用、TNF信号通路等关键信号通路。

Objective:To survey miRNA and the relevant mechanism of Maimendong Tang in the treatment of idiopathic pulmonary fibrosis(IPF)via bioinformatics and network pharmacology.Methods:The active ingredients of Maimendong Tang,and the related target genes and the disease targets of IPF were searched and checked via online database,GSE53845 and disease co-expressed genes were screened through after downloading GSE53845 gene chips from GEO database.Drug-disease intersection targets were taken and uploaded to microRNA online database to predict key gene target-associated microRNA,GO and KEGG analysis of key target genes were carried out using DAVID database,molecular docking analysis was performed by adopting iGEMDOCK,combined with the relevant literature,the mechanism of preventing and treating IPF with Maimendong Tang was analyzed.Results:Maimendong Tang contained 502 active compounds and 1039 predicted targets;43 co-expressed IPF disease gene targets;and the key target MMP3 showed the best binding performance with the compoundβ-carotene.Conclusion:Maimendong Tang could regulate target genes mainly via miR-29 family,let-7 family,miR-26a-5p and other micorRNAs,so as to play the intervention role in the process of IPF,mostly acting on collagen decomposition process,extracellular matrix tissue and extracellular matrix decomposition,and participating in key signal pathways including NF-κB signal pathway,ECM-receptor interaction and TNF signal pathway.