大鼠局灶性脑缺血再灌注后p-CREB、c-fos表达与神经保护  

The expression of p-CREB、c-fos after focal cerebral ischemia-reperfusion and neuroprotection

作　　者：白万胜[1] 陈慧[2] 薛红丽[1] 黎柏源[1] 高国栋[3] 

机构地区：[1]中国人民解放军第323医院神经外科,陕西西安710054 [2]第四军医大学唐都医院检验科,陕西西安710038 [3]第四军医大学唐都医院神经外科,陕西西安710038

出　　处：《中风与神经疾病杂志》2014年第12期1084-1086,共3页Journal of Apoplexy and Nervous Diseases

摘　　要：目的研究p-CREB、c-fos在大鼠局灶性脑缺血再灌注中的表达、尼莫地平的神经保护作用及治疗时间窗。方法颈内动脉尼龙线线栓法MCAO 90 min造模,12只S-D雄性大鼠均分为4组:A组:MCAO 90 min组;B组:MCAO加双侧颈总动脉结扎(BCCAL)30 min组;C组:MCAO加BCCAL 60 min组;D组:MCAO加BCCAL 90 min组。另12只大鼠同上造模并分组,尼莫地平颈内动脉给药。再灌注后24 h脑功能障碍评分,再灌注72 h处死测量脑组织梗死体积,并行HE染色,p-CREB、C-fos免疫组化染色。再选16只动物,同A组造模,并均分为缺血(I-R)组和尼莫地平(Nim)组,两组均在再灌注后2 h,24 h,48 h,72 h分别处死2只动物,行HE染色,p-CREB、C-fos免疫组化染色。结果 HE染色示尼莫地平干预后半暗区神经元损伤明显减轻;再灌注24 h后A^D组神经功能障碍依次加重;与I-R组相比,除D组外,Nim组均较I-R相应组梗死体积小,缺血半暗带边缘区p-CREB表达增强(P<0.05);Nim组半暗带边缘区c-fos表达与I-R组比较无统计学差异。再灌注2 h后p-CREB大量表达,24 h达高峰,后缓慢下降;c-fos 2 h升高,24 h达高峰,72 h明显下降。结论早期尼莫地平动脉给药对轻度/中度脑缺血再灌注损伤治疗效果较好;CREB磷酸化后在脑缺血损伤中的神经元存活起着重要作用;c-fos基因参与了脑缺血的信号转导。Objective To investigate p-CRE.B, c-los expressions following focal cerebral ischemia- reperfusion of rat, to study neuroprotection and therapeutic time window of nimodipine for ischemia-reperfusion. Methods 90 min middle cerebral artery occlusion （MCAO） models were carried out by suture method with nylon monofilament inserted via the internal carotid. 12 male S-D rats were divided into four groups equally ： （A） 90 min MCAO ; （B） 90 rain MCAO with 30 min bilateral common carotid artery ligation （BCCAL） ; （C） 90 min MCAO with 60 min BCCAL; （D） 90 min MCAO with 90 min BCCAL. Another 12 rats were developed into MCAO and divided into 4 groups, simultaneously intracarotid infused with nimodipine. The neurological outcomes were evaluated 24 h after the reperfusion in all animals. The brain infarct volumes were assessed after 72 hour of reperfusion, HE staining,p-CREB and e-fos expressions were detected by immonohistochemistry methods. In addition, 16 animals were developed into 90 rain MCAO and equally divided into two groups, ischemia （I-R） and treatment （Nim） groups. At 2 h,24 b,48 h and 72 h following reperfusion,rats were killed and above stainings were performed. Results HE Staining showed nimodipine could reduce penumbra neuron damages. After 24 h of reperfusion, neurological dysfuctions aggravated taking turns from A to D. Except that of group D, infarct volumes of Nim groups （ A, B, C） were notably decreased compared with that of I-R groups （ P 〈 0.05 ） , p-CREB in marginal penumbra area of Nim groups were more expressed than those regions of I-R groups （P 〈 0.05 ） ,but c-fos expressions in Nim groups had no signif- icance compared with those in I-R groups. After reperfusion, p-CREB clearly expressed at 2 h, peaked at 24 h and began to decrease gradually. C-los strongly increased at 2 h following reperfusion, topped at 24 h and obviously decreased at 72 h. Conclusion Earlier intraearotid nimodipine infusion have better therapeutic efficacy to gentle and middle-d

关 键 词：脑缺血/再灌注 尼莫地平 C-FOS P-CREB 

分 类 号：R743.3[医药卫生—神经病学与精神病学]