小鼠脑缺血再灌注损伤不同时间点基因表达谱的变化研究

Study on Gene Expression Profile at Different Time Points during Cerebral Ischemia Reperfusion in Mice

目的:通过生物信息学方法研究小鼠脑缺血再灌注损伤(CIRI)所致的损伤模型的基因表达谱变化,寻找疾病相关的关键基因。方法:从Gene Expression Omnibus(GEO)中下载关于小鼠脑损伤GSE23160时间序列基因表达谱芯片的原始数据,分析皮质脑组织样本和纹状体脑组织样本在缺血再灌注不同时间点基因表达谱的差异,并对差异表达基因进行GO和KEGG功能富集分析。再通过聚类分析挑取表达趋势明显的差异基因进行免疫细胞浸润分析和关键基因分析。并在大鼠CIRI模型上对显著差异基因进行验证。结果:免疫细胞浸润分析发现CIRI过程中出现肥大细胞和巨噬细胞浸润。CIRI过程中的差异基因主要参与愈伤反应、炎性反应和信号转导通路等。在2个组织样本的不同再灌注时间点Timp1和Gpr84基因表达都发生了显著上调。大鼠CIRI模型进一步验证了Timp1和Gpr84基因的上调表达。结论:Timp1和Gpr84基因可能是脑缺血再灌注过程中的关键基因。

Objective： To explore the key genes related to ischemia reperfusion injury （CIRI） by investigating the gene expression profile of the CIRI model in mice via bioinformatics analysis. Methods： The expression data of GSE23160 time series dataset associated with mouse cerebral injury was downloaded from Gene Expression Omnibus （GEO）. The expression of gene expression profile of cortical brain tissue samples and striatum brain tissue samples at different time points after ischemia-reperfusion was analyzed. The underlying function of differentially expressed genes were predicted by GO and KEGG enrichment analysis. Then the cluster analysis was applied to identify the obvious trend of the differential genes for immune cell infiltration analysis and key genetic analysis. Consequently, the significant differentially expressed genes were verified in ischemia-reperfusion rats. Results： Immune cell infiltration analysis revealed that mast cells and macrophages were infiltrated during CIRI. CIRI gene differences major in the genes involved in callus, inflammatory response,and signal transduction pathway. Moreover, Timp1 and Gpr84 gene expression were significantly up-regulated in both tissues at different reperfusion time. Finally, the up-regulation of Timp1 and Gpr84 genes was further verified in ischemia-reperfusion rats. Conclusion： Our results suggest that Timp1 and Gpr84 genes may be the key genes in CIRI.