丙泊酚对新生小鼠海马组织基因表达谱的影响研究

Effects of propofol exposure on gene expression profiles in the neonatal mouse hippocampus

目的通过生物信息学分析丙泊酚对新生小鼠海马组织基因表达谱的影响,对差异表达基因(DEGs)涉及的功能进行预测,并找出关键的差异表达基因,为后续的机制研究提供理论基础。方法从基因芯片公共数据库(GEO)中获取丙泊酚处理的新生小鼠海马组织基因表达谱数据集GSE106799,以|logFC|>1及FDR<0.05为筛选标准得到DEGs。利用Metascape数据库和DAVID数据库对DGEs进行生物途径(BP)和KEGG通路富集分析,利用Cytoscape软件将DGEs的共表达关系可视化并找出Hub基因,进一步利用GeneMANIA数据库分析蛋白相互作用方式。结果暴露于50 mg/kg丙泊酚3 h后,新生小鼠海马组织中共54个差异表达的基因,其中37个mRNA上调,17个mRNA下调。BP分析结果显示,DEGs主要参与调节MAPK活性、维甲酸信号通路等生物学途径;KEGG分析结果显示,DEGs主要与细胞色素P450酶对外源性物质的代谢、化学致癌作用和酪氨酸代谢等信号通路相关。蛋白质相互作用网络筛选出6个Hub基因:DUSP6、EGR4、TXNIP、PDK4、RGS4和DUSP5;GeneMANIA数据库分析显示,蛋白共表达和预测共占84.38%,是蛋白质相互作用的主要方式。结论丙泊酚能够影响新生小鼠海马组织的基因表达,MAPK通路、维甲酸信号通路、酪氨酸代谢等通路可能参与其致神经毒性作用。

Objective The aim of this study was to explore the effects of propofol exposure on gene expression profiles in the neonatal mouse hippocampus and predict hub genes and pathways of differentially expressed genes(DEGs),providing theoretical basis for further study.Methods The mRNA gene chip dataset GSE106799 of neonatal mouse hippocampus after propofol exposure was downloaded from Gene Expression Omnibus(GEO)public database,the DEGs were obtained based on|logFC|>1 and FDR<0.05.Enrichment analysis of Biological process(BP)and KEGG Pathway were performed by Metascape and DAVID database.Cytoscape was used to visualize the DEGs and find out the hub genes,and GeneMANIA database was utilized for further protein interaction analysis.Results After exposure to propofol(50 mg/kg)for 3 hours,54 DEGs of neonatal mouse hippocampus were screened out,of which 37 mRNAs was up-regulated and 17 mRNAs was down-regulated.BP analysis indicated that several functional pathways,such as inactivation of MAPK activity and signaling by retinoic acid,and KEGG analysis showed the DEGs were associated with metabolism of xenobiotics by cytochrome 450,Chemical carcinogenesis and tyrosine metabolism.DUSP6,EGR4,TXNIP,PDK4,RGS4 and DUSP5 were identified as hub genes after network analysis.GeneMANIA database showed that protein co-expression and prediction were the primary interaction patterns,which accounted for 84.38%.Conclusion Gene expression profiles in the neonatal mouse hippocampus could be altered by propofol,and many pathways,such as MAPK pathway,retinoic acid signaling pathway,and tyrosine metabolism,might be involved in its neurotoxic effects.