基于GEO公共芯片平台探究右美托咪定在大鼠心脏保护中的作用机制  

Identification of candidate mechanism in dexmedetomidine-induced cardioprotection in the rat heart by bioinformatics data mining analysis

作　　者：张继厚 陈权 刘美[2] 尚游 ZHANG Jihou;CHEN Quan;LIU Mei;SHAMG You(Department of Anesthesiology,The First Afiliated Hospital of Jinzhou Medical University,Jinzhou 121001,China;School of Pharmacy,China Medical University,Shenyang 110122,China)

机构地区：[1]锦州医科大学附属第一医院麻醉科,辽宁锦州121000 [2]中国医科大学药学院,辽宁沈阳110122

出　　处：《沈阳药科大学学报》2023年第4期470-477,共8页Journal of Shenyang Pharmaceutical University

基　　金：中国博士后科学基金资助项目(2018M641738)。

摘　　要：目的 通过生物信息学分析右美托咪定(dexmedetomidine, DEX)对大鼠心肌miRNA及mRNA表达谱的影响,构建miRNA-mRNA调控网络,探究DEX在大鼠心脏保护中的作用机制。方法 从公共基因芯片数据平台下载经DEX预处理大鼠缺血再灌注损伤心肌的miRNA基因芯片数据集GSE126105和mRNA数据集GSE126104,筛选差异表达miRNA和mRNA。利用miRWalk数据库对差异表达的miRNA靶基因进行预测。用Metascape数据库对预测靶基因进行基因本体论(gene ontology, GO)和基因组百科全书(kyoto encyclopedia of genes and genomes, KEGG)信号通路富集分析,应用Cytoscape对模块中基因的共表达关系可视化并应用cytoHubba插件筛选Hub基因。结果 给药组大鼠心肌较对照组有5个miRNA和165个mRNA差异表达。将miRWalk数据库预测的miRNAs的靶基因和差异表达的mRNA应用韦恩图取交集,得到42个共同基因,基于此结果构建了miRNA-mRNA调控网络,对此网络基因进行功能富集分析,发现细胞周期增殖、蛋白激酶活性等生物过程(biological process, BP)。筛选出前几个的Hub基因包括Ccnd1、Cdk14和Grm5,主要涉及细胞增殖、RNA转录等过程。结论 通过生物信息学分析发现DEX主要通过调控细胞增殖及炎症通路发挥心肌保护作用,构建的miRNA-mRNA调控网络为进一步探究DEX在心脏I/R损伤及在其他疾病中的作用机制提供参考。Objective To analyze the effects of DEX on rat myocardial miRNA and mRNA expression profiles by using bioinformatics data mining;to construct miRNA-mRNA regulatory network, and to explore the mechanism of dexmedetomidine(DEX) in rat cardioprotection.Methods The miRNA gene chip datasets GSE126105 and mRNA datasets GSE126105 were download from public gene chip data platform(Gene expression omnibus, GEO) for screening differentially expressed miRNA and mRNA.The miRWalk database was used to predict the miRNA target genes.Metascape database was utilized to analyze gene ontology(GO) and KEGG signaling pathway enrichment.Cytoscape was used to visualize the co-expression of genes in the module and predict Hub genes by cytoHubba.Results Compared with the control group, 5 miRNAs and 165 mRNAs were differentially expressed in DEX group.Biological progress of differentially expressed mRNA mainly involves in cell cycle, MAPK pathway, et al.The target genes of miRNAs predicted by miRWalk database and differentially expressed mRNAs were intersected by Venn diagram, and 42 shared genes were obtained, and miRNA-mRNA regulatory network was constructed based on these results.Functional enrichment analysis revealed that biological processes(BP) were mainly involved in cell cycle proliferation and protein kinase activity, etc.The top Hub genes included Ccnd1,Cdk14 and Grm5,which were mainly involved in cell proliferation, RNA transcription and other processes.Conclusion Our study found that DEX plays a protective role in the cardiac muscle mainly by regulating cell proliferation and inflammatory pathways, and the constructed miRNA-mRNA regulatory network provides a reference for further exploring DEX therapeutic role in cardiac I/R damage and other diseases.

关 键 词：右美托咪定 缺血再灌注 miRNA-mRNA网络 生物信息学 

分 类 号：R614[医药卫生—麻醉学]