迷走神经电刺激对大脑中动脉阻断/再灌注大鼠脑损伤及脑组织中p-CREB表达的影响  

Effects of vagus nerve stimulation on cerebral ischemia injury and expression of p-CREB in rat MCAO/reperfusion models

作　　者：郭佳[1] 关智媛 孙守元 金晶[1] 李鸣明[1] 卜玉洁[1] 张廷华[1] 

机构地区：[1]兰州大学第二医院神经内科,兰州730030 [2]兰州大学第二临床医学院,兰州730030

出　　处：《解放军医学杂志》2017年第8期702-706,共5页Medical Journal of Chinese People's Liberation Army

基　　金：2015年度兰州大学第二医院院内博士科研基金(YNBSKYJJ2015-1-29);甘肃省青年科技基金计划项目(1506RJYA246)~~

摘　　要：目的研究迷走神经电刺激(V NS)对大鼠大脑中动脉阻断(M C AO)/再灌注大鼠脑损伤的影响及其机制。方法健康成年雄性SD大鼠24只,随机分为两组:MCAO/再灌注组(MCAO组,n=12)大鼠仅行MCAO/再灌注,MCAO/再灌注+VNS组(MCAO+VNS组,n=12)大鼠在接受MCAO/再灌注的同时行右侧颈部迷走神经电刺激。两组大鼠均在再灌注24h后采用Zea Longa评分法行神经功能评分,通过TTC实验检测脑梗死区体积,TUNEL法检测脑损伤区细胞凋亡情况,Western blotting检测脑损伤区组织中c AMP反应元件结合蛋白(CREB)、磷酸化CREB(p-CREB)的表达,免疫组化染色检测脑损伤区细胞中Bcl-2和Bax蛋白的表达。结果与MCAO组相比,MCAO+VNS组大鼠神经功能改善(P<0.01),脑梗死体积减少(P<0.01),脑组织细胞凋亡减少(P<0.01);MCAO+VNS组大鼠脑梗死区组织中p-CREB蛋白表达(P<0.01)和Bcl-2的阳性细胞数量增加(P<0.01),Bax阳性细胞数量减少(P<0.01),但CREB蛋白表达量无明显差异(P>0.05)。结论 VNS可显著改善MCAO/再灌注大鼠神经功能,降低脑梗死体积,其机制可能与提高p-CREB蛋白表达有关。Objective To investigate the effects of vagus nerve electrostimulation （VNS） on the brain damage of rat middle cerebral artery occlusion （MCAO）/reperfusion model and its mechanism. Methods Twenty four adult male SD rats were randomly divided into two groups （12 each）： MCAO/reperfusion group （MCAO group） and MCAO/reperfusion＋VNS group （MCAO＋VNS group）. Subsequently, the neurological function deficit was determined by neurological scoring according to Zea Long scoring method 24h after MCAO/reperfusion. The cerebral infarction volume was determined by TTC assay. The cell apoptosis in brain damage zone was determined by TUNEL assay. Then, the effect of VNS on cAMP response element binding protein （CREB） and p-CREB protein expression was determined by Western blotting. The effect of VNS on Bcl-2 and Bax expression was determined by immunohistochemistry assay. Results Compared with MCAO group, VNS significantly inhibited MCAO-induced neurological deficit （P〈0.01）, decreased brain infarct volume （P〈0.01） and cell apoptosis （P〈0.01）, increased the expression of p-CREB protein （P〈0.01） and the number of Bcl-2-position cells （P〈0.01） together with decreasing the number of Bax-position cells （P〈0.01）. However, VNS did not affect the expression of CREB protein （P〉0.05）. Conclusion VNS may ameliorate MCAO-induced neurological deficit and decrease brain infarct volume, which may be related to the promotion of p-CREB protein expression level.

关 键 词：迷走神经电刺激 CAMP反应元件结合蛋白 大脑中动脉阻断 细胞凋亡 

分 类 号：R743.3[医药卫生—神经病学与精神病学]