儿童溃疡性结肠炎的关键基因筛选及潜在治疗药物预测  

Screening of hub genes in children with ulcerative colitis and prediction of potential therapeutic drugs

作　　者：韩雨 马英华 姜锡娟 安志华 秦亚彬 赵宜乐 张古英[1] 安娜[1] HAN Yu;MA Ying-hua;JIANG Xi-juan;AN Zhi-hua;QIN Ya-bin;ZHAO Yi-le;ZHANG Gu-ying;AN Na(Department of Pharmacy,Hebei Children’s Hospital,Shijiazhuang 050031)

机构地区：[1]河北省儿童医院药学部,石家庄050031

出　　处：《中南药学》2024年第10期2680-2685,共6页Central South Pharmacy

基　　金：河北省医学科学研究课题计划(No.20211391)。

摘　　要：目的筛选儿童溃疡性结肠炎(UC)结肠组织中的关键的差异基因,预测潜在的治疗药物,并探究药物发挥作用的可能机制。方法基于GEO数据库中的GSE126124测序数据筛选儿童UC的关键基因。采用葡聚糖硫酸钠构建小鼠急性UC模型,通过qPCR检测关键基因的mRNA表达水平。通过Connectivity Map(CMAP)在线数据库筛选潜在的UC治疗药物,构建药物-疾病靶点的PPI网络并提取显著基因模块。通过GO分析和KEGG通路富集分析探究药物发挥作用的可能机制。结果在UC患儿结肠组织共筛选出52个差异基因,其中关键基因DEFA6、DEFA5、CXCL1、MMP1、MMP7、DEFB4A、SAA1、LCN2 mRNA水平在UC小鼠模型中显著升高。通过CMAP筛选得到的天然活性成分樱黄素可能通过调控白细胞介素(IL)-17信号通路、核转录因子(NF)-κB等信号通路发挥抗UC的治疗作用。结论UC患儿组织中的差异基因可能是潜在的治疗靶点,樱黄素可能是UC潜在的治疗药物。Objective To identify differentially expressed genes(DEGs)in the colonic tissues of children with ulcerative colitis(UC)and to predict potential therapeutic drugs and related mechanism.Methods GSE126124 dataset from the GEO database was used to comprehensively screen for hub genes associated with UC in children.The acute UC mouse model was established by the dextran sulfate sodium(DSS),and the mRNA expression levels of hub genes were detected by qPCR.Subsequently,the Connectivity Map(CMAP)database was leveraged to identify candidate therapeutic drugs for UC.A protein-protein interaction network was established to elucidate the interactions between drug targets and disease-related genes,and the obvious gene module was extracted for further analysis.Go analysis and KEGG pathway enrichment analysis were used to determine the potential mechanism of predicted drug candidates.Results Totally 52 DEGs were identified in the colon tissues of children with UC.Notably,the mRNA levels of the hub genes,including DEFA6,DEFA5,CXCL1,MMP1,MMP7,DEFB4A,SAA1 and LCN2,were markedly elevated in the DSS-induced UC model.Prunetin,a natural active component screened by CMAP,exerted a therapeutic effect on UC by regulating IL-17,NF-κB and other signal pathways.Conclusion The identified DEGs may serve as potential therapeutic targets for UC.Furthermore,prunetin may become as a promising therapeutic drug for the treatment of UC.

关 键 词：溃疡性结肠炎 炎性肠病 樱黄素 NF-ΚB IL-17 

分 类 号：R96[医药卫生—药理学]