下调IGF-1通过CREB信号通路失活间接加重大鼠脑缺血损伤  

Downregulation of IGF-1 inactivated CREB signal pathway and indirectly aggravated cerebral ischemic injury in rats

作　　者：闵晓黎[1,2] 王廷勇[3] 刘佳[1] 王廷华[1] 

机构地区：[1]昆明医科大学神经科学研究所,云南昆明650500 [2]云南中医学院临床学院/第一附属医院,云南昆明650500 [3]四川大学,四川成都610065

出　　处：《中风与神经疾病杂志》2015年第10期872-876,共5页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金项目(No.81471268);云南省科技计划项目(No.2013FZ199)

摘　　要：目的探讨MEK/ERK/CREB信号通路是否介导IGF-1在大鼠脑缺血中的调控作用。方法成年雄性SD大鼠使用MACO线栓法建立永久性局灶性脑缺血模型,进行m NSS神经功能缺损评分,脑缺血48 h时进行TTC染色观察脑梗死情况、末端标记(TUNEL)法检测细胞凋亡,并利用实时荧光定量PCR和Western blot检测缺血同侧大脑皮质内IGF-1及下游信号分子MEK、ERK1/2和CREB的mRNA和蛋白表达变化,及其磷酸化水平的变化情况。结果脑缺血组大鼠m NSS评分、细胞凋亡百分比均明显高于假手术组,缺血大脑皮质内IGF-1表达下调,MEK、ERK1/2和CREB的基因水平下降,MEK、ERK1/2的蛋白水平及其磷酸化蛋白水平均明显降低。结论本实验结果表明永久性局灶性脑缺血早期大鼠皮质内下调的IGF-1,可以通过负调控MEK/ERK/CREB促存活信号通路,间接加重大鼠脑缺血性损伤。Objective To investigate whether MEK / ERK / CREB signaling pathway mediated by IGF-1 or not in cerebral ischemia of rats. Methods Using MACO suture method established the permanent focal cerebral ischemia model of adult male SD rats,the neurological deficits were assessed by m NSS score. After MACO48 h,cerebral infarction areas were observed with TTC staining,and the cell apoptosis evaluated by end labeling（ TUNEL） assay. Then the mRNA expression of IGF-1 and the downstream signaling molecules MEK,ERK and CREB in ischemia ipsilateral cortex of rats were detected by real-time fluorescent quantitative PCR,and the protein expressing levels of MEK,ERK1 /2 and the changes of their phosphorylation level were detected by western blot. Results The m NSS score and apoptotic cells percentage in cerebral ischemia rats were significantly increased than sham operation group. The expression of IGF-1,MEK,ERK1 /2,CREB mRNA and protein levels were robustly decreased,and their phosphorylation levels were also decreased. Conclusion IGF-1 was downregulated within rats＇ cortices in the early stage of ischemia,through inactivation of MEK / ERK / CREB signaling pathway,indirectly aggravated the cerebral ischemic injury in rats.

关 键 词：脑缺血 信号通路 IGF-1 MEK ERK CREB 凋亡 

分 类 号：R743.3[医药卫生—神经病学与精神病学]