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

doi:10.3969/j.issn.1673-5765.2017.11.006

中国卒中杂志 ›› 2017, Vol. 12 ›› Issue (11): 1000-1004.DOI: 10.3969/j.issn.1673-5765.2017.11.006

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

董雯，王拥军

1100050 北京首都医科大学附属北京天坛医院临床医学研究实验室
2首都医科大学附属北京天坛医院神经病学中心；国家神经系统疾病临床医学研究中心；北京脑重大疾病研究院脑卒中研究所；脑血管病转化医学北京市重点实验室

收稿日期:2017-03-17 出版日期:2017-11-20 发布日期:2017-11-20
通讯作者: 王拥军 yongjunwang111@aliyun.com
基金资助:
国家重点研发计划（2017YFC1307501）
首都医科大学附属北京天坛医院青年科研基金项目（No.2016-YQN-19）
国家自然科学基金（81701138）

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

Received:2017-03-17 Online:2017-11-20 Published:2017-11-20

摘要/Abstract

摘要：

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。

文章导读： 本文利用全基因组表达谱芯片筛查，发现Flnc 和Ccnd1基因在小鼠脑缺血再灌注后星形胶质细胞活化过程中具有重要作用。

关键词: 脑缺血再灌注; 基因芯片; 差异表达; 信号通路

Abstract:

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 astrocytesfollowing 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.

Key words: Cerebral ischemia/reperfusion; Gene microarray; Differential expression; Signal pathway

董雯，王拥军. 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[J]. 中国卒中杂志, 2017, 12(11): 1000-1004.

DONG Wen, WANG Yong-Jun. Gene Microarray Analysis of Astrocytes in Acute Ischemic Stroke Mice Based on Gene Expression Omnibus[J]. Chinese Journal of Stroke, 2017, 12(11): 1000-1004.

参考文献

[1] WANG W，JIANG B，SUN H，et al. Prevalence，

incidence，and mortality of stroke in China：results

from a nationwide population-based survey of 480

687 adults[J]. Circulation，2017，35（8）：759-771.

[2] FAVATEAS，YOUNGER D S. Epidemiology of

ischemic stroke[J]. Neurologic clinics，2016，34（4）：

967-980.

[3] HACKEW，KASTEM，BLUHMKIE，et al.

Thrombolysis with alteplase 3 to 4. 5 hours after

acute ischemic stroke[J]. N Engl J Med，2008，359

（13）：1317-1329.

[4] ARAI K，LOK J，GUO S，et al. Cellular

mechanisms of neurovascular damage and repair

after stroke[J]. J Chil Neuro，2011，26（9）：1193-

1198.

[5] SUN Y，LIU WZ，LIU T，et al. Signaling pathway

of MAPK/ERK in cell proliferation，differentiation，

migration，senescence and apoptosis[J]. J Recept

Signal Transduct Res，2015，35（6）：600-604.

[6] YAOB，WANGS，XIAOP，et al. MAPK signaling

pathways in eye wounds：multifunction and

cooperation[J]. Exp Cell Res，2017，359（1）：10-16.

[7] KATCHANOVJ，HARMSC，GERTZK，et al. Mild

cerebral ischemia induces loss of cyclin-dependent

kinase inhibitors and activation of cell cycle

machinery before delayed neuronal cell death[J]. J

Neurosci，2001，21（14）：5045-5053.

[8] KATOH，TAKAHASHIA，ITOYAMAY. Cell

cycle protein expression in proliferating microglia

and astrocytes following transient global cerebral

ischemia in the rat[J]. Brain Res Bull，2003，60（3）：

215-221.

[9] ZHUZ，ZHANGQ，YUZ，et al. Inhibiting cell cycle

progression reduces reactive astrogliosis initiated by

scratch injury in vitro and by cerebral ischemia in

vivo[J]. Glia，2007，55（5）：546-58.

[10] STOSSELTP，CONDEELISJ，COOLEYL，et

al. Filamins as integrators of cell mechanics and

signalling[J]. Nature reviews. Nat Rev Mol Cell Biol，

2001，2（2）：138-145.

[11] ZHOUAX，HARTWIGJH，AKYUREKLM.

Filamins in cell signaling，transcription and organ

development[J]. Trends Cell Biol，2010，20（2）：

113-123.

[12] XIEZ，XUW，DAVIEEW，et al. Molecular

cloning of human ABPL，an actin-binding protein

homologue[J]. Biochem Biophys Res Commun，1998，

251（3）：914-919.

[13] PUDASR，KIEMATR，BUTLERPJ，et al. Structural

basis for vertebrate filamin dimerization[J]. Structure，

2005，13（1）：111-119.

[14] ADACHI-HAYAMAM，ADACHIA，

SHINOZAKIN，et al. Circulating anti-filamin C

autoantibody as a potential serum biomarker for lowgrade

gliomas[J]. BMC cancer，2014，14：452.

[15] NAKAMURAF，STOSSELTP，HARTWIGJH. The

filamins：organizers of cell structure and function[J].

Cell Adh Migr，2011，5（2）：160-169.

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

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

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