目的 通过microRNAs差异分析、网络药理学及分子对接技术,探讨益母草治疗宫腔粘连(intrauterine adhesion,IUA)的潜在作用靶点及相关机制.方法 基于GEO(gene expression omnibus)数据库筛选IUA与健康者的差异 miRNA,经multiMiR进行靶基因预测.通过TCMSP(traditional Chinese medicine systems pharmacology)数据库检索益母草有效活性成分及相关靶点,并与miRNA靶基因取交集.利用String平台进行蛋白质互作分析,利用cytoNCA筛选关键靶点.基于R语言进行基因本体(gene ontology,GO)和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析.利用CB-dock2对关键靶点和活性成分进行分子对接.结果 共筛选出与IUA相关的差异miRNA 43个,经靶基因预测后与IUA共有13个交集靶点,GO及KEGG富集分析结果显示,益母草治疗IUA作用机制主要与细胞衰老、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、PI3K-Akt信号通路等有关.益母草3个特征性活性成分是花生四烯酸、山奈酚、槲皮素,可与蛋白互作网络中相对应的靶点蛋白细胞周期蛋白依赖性激酶4(cyclin-dependent kinase 4,CDK4)、芳香烃受体(aryl hydrocarbon receptor,AHR)、原癌基因c-myc编码转录因子、血管内皮生长因子(vascular endothelial growth factor,VEGF)进行分子对接,主要活性成分能够与核心靶点结合,并展现出较好的亲和力.结论 益母草治疗IUA是多成分、多靶点、多通路相互作用的结果,进一步证实了益母草治疗IUA的科学性及有效性,为后续实验提供了研究思路.
Exploring the mechanism of Leonurus in treating intrauterine adhesions:A study based on microRNAs differential analysis and network pharmacology
Objective:To investigate potential targets and related mechanisms of Leonurus for treating intrauterine adhesion(IUA)by microRNAs differential analysis,network pharmacology and molecular docking techniques.Methods:Different mirnas of IUA and healthy people were screened based on GEO database,and target genes were predicted by multiMiR.TCMSP database was used to search the active ingredients and related targets of Leonurus,and the intersection with miRNA target genes was obtained.The STRING platform was used for protein interaction analysis,and cytoNCA was used to screen key targets.GO and KEGG analysis was based on R language.CB-dock2 was used for molecular docking of key targets and active ingredients.Results:A total of 43 different mirnas related to IUA were screened,and 13 intersection targets of IUA were predicted by target genes.GO and KEGG enrichment analysis results showed that the mechanism of Leonurus treatment of IUA was mainly related to cell aging,MAPK signaling pathway,PI3K-Akt signaling pathway,etc.The three characteristic active components arachidonic acid,kaempferol,quercetin and corresponding target proteins(CDK4,AHR,MYC,VEGFA)in the protein interaction network were docked,and the molecular docking results showed that the main active components could bind to the core target,showing a good affinity.Conclusion:The results of multi-component,multi-target and multi-pathway interaction of Leonurus in the treatment of IUA further confirmed the scientificity and effectiveness of Leonurus in the treatment of IUA,thus providing research ideas for the follow-up experiment setting.
NETL
NSTL
万方数据
维普
