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目的分析新生大鼠缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)后7周大脑皮层与对照组脑皮层的基因表达差异,探讨其生物学意义。方法从基因表达数据库(Gene Expression Omnibus database,GEO)中获取新生Wista大鼠缺氧缺血性脑损伤后7周大脑皮层基因表达芯片数据集GSE37777。该数据集共8个样本,4个样本为HIBD组,4个样本为对照组。采用R软件包对数据做预处理和差异性表达基因(differentiallyexpressed genes,DEGs)的筛选,应用Cytoscape插件ClueGO+Cluepedia构建DEGs功能分组通路网络。通过相互作用基因库检索工具(Search Tool for the Retrieval of Interacting Genes,STRING)数据库和Cytoscape软件进行DEGs的蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络分析。结果 HIBD组共发现973DEGs,其中599个基因表达上调,374个基因表达下调。DEGs功能分组通路网络分析显示Hedgehog信号通路是最显著的差异性表达基因通路。HIBD组中Hedgehog通路相关基因Shh及Dhh表达上调,Wnt通路相关基因Wnt1、Wnt2B及Wnt5表达上调。PPI网络分析显示Ccnd1、Shh、Ret及Gli3是主要的中心蛋白,Shh和Ret表达上调,Ccnd1和Gli3表达下调。结论生物信息学分析显示,新生大鼠HIBD后7周脑皮层可能存在Hedgehog和Wnt信号通路的激活,与细胞修复相关的蛋白Shh及Ret的表达上调。新生大鼠HIBD 7周后脑皮层可能存在持续修复过程。
Objective To analyze the difference of gene expression between cerebral cortex and cerebral cortex of cerebral cortex 7 weeks after hypoxic-ischemic brain damage (HIBD) in neonatal rats, and to explore its biological significance. Methods The gene expression microarray data GSE37777 of cerebral cortex were obtained from neonatal Wistar rats 7 weeks after hypoxic-ischemic brain damage from Gene Expression Omnibus database (GEO). The data set contains 8 samples, 4 samples are HIBD group and 4 samples are control group. The data were preprocessed and differentially expressed genes (DEGs) were screened by R software package, and DEGs functional grouping network was constructed by Cytoscape plug-in ClueGO + Cluepedia. The protein-protein interaction (PPI) network of DEGs was analyzed by the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. Results 973 DEGs were found in HIBD group, of which 599 genes were up-regulated and 374 genes were down-regulated. Network analysis of DEGs functional grouping pathway showed that Hedgehog signaling pathway was the most significant differentially expressed gene pathway. Hedgehog pathway related genes Shh and Dhh were upregulated in HIBD group, and Wnt1, Wnt2B and Wnt5 were up-regulated. PPI network analysis showed that Ccnd1, Shh, Ret and Gli3 are the major central proteins, Shh and Ret are up-regulated, while Ccnd1 and Gli3 are down-regulated. Conclusions Bioinformatics analysis showed that there may be activation of Hedgehog and Wnt signaling in the cerebral cortex 7 weeks after HIBD in neonatal rats, and the expressions of Shh and Ret related to cell repair were up-regulated. Neonatal rats HIBD 7 weeks after the cerebral cortex may exist continuous repair process.