新生大鼠缺氧缺血性脑损伤后差异性表达基因的生物信息学分析

Bioinformatic Analysis of Differentially Expressed Genes Involved in the Post-hypoxic Ischemic Brain Damage of Newborn Rats

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 differentially expressed genes （DEGs） in cerebral cortices of rats which were seven weeks after neonatal hypoxic ischemic brain damage （HIBD） and elucidate the biological significance of the DEGs. Methods The gene expression profile of GSE37777, including 4 HI samples subjected to HIBD and 4 normal controls, was downloaded from the Gene Expression Omnibus database （GEO）. DEGs were screened using the R package in HIBD groups compared with normal controls. Pathway enrichment analysis was carried out using the Cytoscape plug-in ClueGO＋ Cluepedia and a functionally grouped pathway network of DEGs was constructed and analyzed. Besides, the protein-protein interaction （PPI） network was constructed with the Search Tool for the Retrieval of Interacting Genes （STRING） database and visualized using Cytoscape. Results A total of 973 DEGs were identified in HIBD group compared with the control group, including 599 up-regulated and 374 down-regulated genes. Furthermore, a functionally grouped pathway network of DEGs was constructed and hedgehog signaling pathway were identified. Shh and Dhh which were Hedgehog signaling pathway-related genes and the Wnt signaling pathway-related genes Wntl, Wnt2B, and Wnt5 were up-regulated in HIBD group. Furthermore, Ccndl, Shh, Ret and Gli3 were hub proteins in the PPI network and up-regulated Shh and Dhh, down-regulated Ccndl and Gli3 were noticed. Conclusion Our results showed that Hedgehog and Wnt signaling pathway may be activated HIBD group. Additionally, Shh and Ret which were related to the repair process of brain damage were up-regulated. Continuous repair process may exist in the cerebral cortices of rats which were seven weeks after neonatal HIBD.