右美托咪定对全脑缺血/再灌注大鼠海马CA1区神经元GluR2蛋白表达的影响  

The effect of dexmedetomidine on the expression of GluR2 protein in hippocampal CA1 neurons of rats subjected to global ischemia/reperfusion

作　　者：支利军 王绍娴 于常州[1] 许鹏程[1] 颜学军[2] Zhi Lijun Wang Shaoxian Yu Changzhou Xu Pengcheng Yan Xuejun(Jiangsu Province Key Laboratory of Anesthesiology Xuzhou Medical Colloge, Jiangsu Province Key Laboratory of Anesthesiology and Analgesia Application Technology, Xuzhou 221004, China Department of Anesthesiology, the Affiliated Huai＇an Hospital of Xuzhou Medical College, Huai＇an 223002, China)

机构地区：[1]江苏省麻醉与镇痛应用技术重点实验室,徐州医学院江苏省麻醉学重点实验室,221004 [2]徐州医学院附属淮安医院麻醉科,淮安223002

出　　处：《国际麻醉学与复苏杂志》2016年第1期31-36,共6页International Journal of Anesthesiology and Resuscitation

基　　金：徐州医学院院长基金（2012XJZ18）;淮安市科技局计划项目（HAS2013009）;淮安市委组织部533英才工程项目（201200122）

摘　　要：目的 探讨右美托咪定（dexmedetomidine,Dex）预处理对全脑缺血/再灌注（ischemia/reperfusion,I/R）大鼠海马CA1区神经元GluR2蛋白[α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（α-amino-3-hydroxy-5-methyl4-isoxa-zolep-propionate acid,AMPA）受体中限制Ca2＋通透的亚基]表达以及学习记忆能力的影响. 方法 按照随机数字表法将48只雄性SD大鼠分为4组（每组12只）：假手术组（S组）,I/R组,Dex组（D组）,育亨宾＋Dex组（YD组）.使用四血管阻断法制作脑I/R模型,脑缺血5 min后行再灌注.D组于缺血前30 min腹腔注射Dex 100 μg/kg,YD组于对应时间点同时腹腔注射Dex 100 μg/kg和育亨宾0.1 mg/kg,S组和I/R组腹腔注射等量生理盐水.各组于再灌注后7d进行Morris水迷宫实验,测试各组大鼠的空间学习记忆能力.于再灌注72 h时,处死大鼠并分离海马CA1区,应用Western blot法测定GluR2蛋白的表达. 结果 与S组比较,I/R组大鼠的逃避潜伏期明显延长（P＜0.05）、停留目标象限时间[（32.1±5.0）s比（48.7±5.5）s]和穿越平台次数[（1.5±0.8）次比（5.0±1.2）次]明显减少（P＜0.05）;与I/R组比较,D组的逃避潜伏期明显缩短（P＜0.05）,停留目标象限时间[（40.6±2.1）s比（32.1±5.0）s]和穿越平台次数[（3.3 ±0.5）次比（1.5±0.8）次]明显增加（P＜0.05）;与D组比较,YD组的逃避潜伏期明显延长,停留目标象限时间[（32.2±6.0）s比（40.6±2.1）s]和穿越平台次数[（1.6±0.8）次比（3.3±0.5）次]明显减少（P＜0.05）;I/R组与YD组比较,差异无统计学意义（P＞0.05）;I/R 72 h,I/R组大鼠海马CA1区GluR2蛋白表达显著下调（P＜0.01）,D组GluR2蛋白表达下调比I/R组明显减小（P＜0.05）,YD组GluR2蛋白表达水平明显低于D组（P＜0.05）,YD组与I/R组比较,差异无统计学意义（P＞0.05）. 结论 Dex可减轻大鼠全脑I/R的学习记忆能力障碍,其机制可能与抑制脑缺血后海马CA1区GluR2蛋白表达的下调有Objective To investigate the effects of dexmedetomidine （Dex） on learning,memory ability and GluR2 [the subunit that restricts Ca2＋ permeability of a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid （AMPA） receptors] protein expression in hippocampal CA1 neurons of rats subjected to global ischemia/reperfusion （I/R）.Methods Forty-eight male SD rats were randomly divided into four groups（n=12）：group sham operation （groupS）,group global I/R （group I/R）,global I/R＋Dex 100 μg/kg （gnoupD）,yohimbine 0.1 mg/kg＋Dex 100 μg/kg＋global I/R （group YD）.The model of global ischemia was established with method of 4-vessel occlusion with five minutes followed by reperfusion.Yohimbine and/or Dex was administered intraperitoneally 30 min before ischemia.While eaqual volume of normal saline was injected intraperitoneally in group S and I/R respectively.Spatial learning and memory function of rats in each group was tested by Morris water maze after seven days of reperfusion.To examine GluR2 protein abundance,Western blot analysis was performed on samples isolated from hippocampal CA1 subfield from each group at 72 h after reperfusion.Results Compared with group S,the escape latency in group I/R was significantly longer （P〈0.05）,and the time in the target quadrant of the platform[（32.1±5.0） s vs （48.7±5.5） s] and times across the platform[（1.5±0.8） vs（5.0±1.2）] in group I/R were significantly decreased （P〈0.05）.Compared with group I/R,the escape latency in group D was significantly decreased （P〈0.05）,and the time in the target quadrant of the platform [（40.6±2.1） s vs （32.1±5.0） s] and times across the platform [（3.3±0.5） vs （1.5±0.8）] in group D were significantly increased（P〈0.05）.Compared with group D,the escape latency in group YD was significantly increased（P〈0.05）,and the time in the target quadrant of the platform[（32.2±6.0） s vs （40.6±2.1） s] and times across the platform[（1.6±0.8） vs （3.3±0.5�

关 键 词：右美托咪定 缺血/再灌注损伤 海马 CA1区 GluR2蛋白 

分 类 号：R614[医药卫生—麻醉学]