基于基因表达谱筛查小鼠脑缺血再灌注后星形胶质细胞活化相关基因

目的 利用全基因组表达谱芯片筛查脑缺血再灌注后星形胶质细胞中起关键作用的信号通路，并对 星形胶质细胞活化过程中可能参与的关键基因进行分析。 方法 从美国基因表达汇编（gene e xpression o mnibus，GEO）数据库中选取小鼠星形胶质细胞基因表 达谱芯片（Affymetrix Gene Chip Mouse Genome 430 2.0 Arrays）数据8张。小鼠分为脑缺血再灌注组 （脑缺血1 h再灌注24 h）和假手术组，每组4只。筛选差异表达基因，并进行信号通路分析，筛选核心 信号通路，分析具有重要调控作用的基因。 结果 共筛查出1966个在脑缺血再灌注后星形胶质细胞中差异表达的基因，其中有1210个基因表达 上调，756个基因表达下调。信号通路分析得到154个差异表达的信号通路。进一步分析发现，在脑 缺血再灌注后参与星形胶质细胞活化的关键信号通路主要有丝裂原活化蛋白激酶（mitogen-activated protein kinases，MAPK）信号通路、凋亡（apoptosis）、细胞周期（cell cycle）和p53信号通路。对信号通路 中差异基因的分析发现，Flnc 和Ccnd1基因在脑缺血再灌注后星形胶质细胞活化过程中具有重要作用。 结论 脑缺血再灌注后星形胶质细胞中有大量基因表达异常。通过对差异基因的分析，筛选出脑缺 血再灌注损伤过程中潜在的发挥重要调控作用的新靶点。

Gene Microarray Analysis of Astrocytes in Acute Ischemic Stroke Mice Based on Gene Expression Omnibus

Objective To explore the signal pathway which played a key role in astrocytes following cerebral ischemia/reperfusion by microarray, and to analyze the key genes which might involve in the activation process of astrocytes. Methods Data of 8 chips of astrocytes from mouse brain of Affymetrix Gene Chip Mouse Genome 430 2.0 arrays were collected from Gene Expression Omnibus (GEO) database. Eight mice were divided into two groups: Experimental group (Ischemia with 60 min MCAO plus 24 h reperfusion, n=4)and Sham operation group(n=4).The differentially expressed genes were detected,then the signal pathways were analyzed to screen the key signal pathway and analyze the genes which played an important role in regulation. Results A total of 1966 genes were determined as differential genes in astrocytes from acute ischemia/reperfusion mice, among which, 1210 genes expression were up regulated and 756 genes were down regulated. Pathway analysis determined 154 differential pathways. Further analysis found that four pathway including mitogen-activated protein kinases (MAPK) pathway, apoptosis, cell cycle and p53 pathway, which played an important role in activation process of astrocytes following ischemia/reperfusion.Moreover,Flnc1 and Ccnd1 were key genes in activation process of astrocytes in response to ischemia/reperfusion. Conclusion Acute cerebral ischemia/reperfusion resulted in abundant differential expressed genes that played important roles in activation process of astrocytes. Through analyzing the differential genes, the new targets which potentially play the important regulation role in ischemia/reperfusion injury could be screened.