CGRP及NGF对局灶性脑缺血再灌注大鼠海马cAMP反应元件结合蛋白磷酸化的影响  

EFFECT OF CGRP AND NGF ON THE PHOSPHORYLATION OF CREB PROTEIN IN RAT HIPPOCAMPUS DURING FOCAL CEREBRAL ISCHEMIA/REPERFUSION

作　　者：张正洪[1] 席刚明[1] 李文春[2] 黄铁柱[2] 方秀斌[3] 

机构地区：[1]郧阳医学院附属人民医院神经内科 [2]郧阳医学院解剖学教研室,十堰442000 [3]中国医科大学基础医学院神经生物学教研室,沈阳110001

出　　处：《解剖学报》2008年第2期165-169,共5页Acta Anatomica Sinica

基　　金：辽宁省自然科学基金(619019);十堰市科技攻关[十科发(2007)19号]资助项目

摘　　要：目的探讨外源性降钙素基因相关肽(CGRP)及神经生长因子(NGF)对局灶性脑缺血再灌注大鼠海马cAMP反应元件结合蛋白(CREB)和磷酸化CREB(p-CREB)表达的影响。方法用线栓法阻塞大鼠右侧大脑中动脉制作局灶性脑缺血再灌注模型,应用免疫组织化学SABC法、Western blotting和图像分析方法检测大鼠手术侧海马CA1区CREB和p-CREB表达。结果缺血再灌注组海马CA1区CREB表达较假手术组减少,p-CREB表达高于假手术组(P<0.05);CGRP组和NGF组CA1区的CREB和p-CREB表达均高于缺血再灌注组(P<0.05);CGRP与NGF联合应用时CREB和p-CREB表达分别高于CGRP组和NGF组(P<0.05)。结论CGRP及NGF上调局灶性脑缺血再灌注大鼠海马CREB和p-CREB的表达,CGRP与NGF联合应用则作用更强,CGRP及NGF对缺血神经元的保护作用可能是通过上调神经元内CREB和p-CREB来实现的,CGRP与NGF对缺血神经元的保护有协同作用。Objective To investigate the effect of exogenous calcitonin gene related peptide（CGRP） and nerve growth factor（NGF） on the expression of cyclic AMP response element binding protein（CREB） and phosphorylated CREB（p-CREB） in rat hippocampus during focal cerebral ischemia/reperfusion（I/R）. Methods Focal cerebral ischemia/reperfusion model was set up by occlusion of the right middle cerebral artery using the intraluminal suture method.The expression of CREB and p-CREB in the right hippocampus were detected with immunohistochemistrical SABC method and Western blotting.The immunoreactive positive products were analyzed by image analysis system. Results The expression of CREB decreased in I/R group as compared with sham group in right hippocampus,but the expression of p-CREB was higher in I/R group than that in sham group（P〈0.05）.The average absorbence（A） of CREB and p-CREB positive products in CGRP group and NGF group were higher than that in I/R group（P〈0.05）.Furthermore,the expression of CREB and p-CREB was even higher under the combined treatment of CGRP and NGF than that in CGRP group and NGF group respectively（P〈0.05）.Conclusion CREB may be involved in the mechanism of protective effect of CGRP and NGF on ischemic neurons.CGRP and NGF may have coordinated protective effect on the ischemic neurons,and they may cooperate with each other to promote the recovery of the ischemic neurons.

关 键 词：脑缺血 降钙素基因相关肽 神经生长因子 海马 c—AMP反应元件结合蛋白 免疫组织化学 免疫印迹法 大鼠 

分 类 号：R743[医药卫生—神经病学与精神病学] R322.81[医药卫生—临床医学]