丰富环境对缺氧缺血性脑损伤幼鼠海马区pCREB及凋亡调控基因表达的影响  

Effect of environmental enrichment on expressions of phosphorylated cAMP response element binding protein and apoptotic regulated genes in the hippocampus of immature rats with hypoxic-ischemic brain damage

作　　者：苑爱云 侯梅 单若冰 刘秋燕 宫阳阳 孙向峰 

机构地区：[1]青岛市妇女儿童医院神经康复科,266034 [2]青岛市妇女儿童医院新生儿科,266034

出　　处：《中华神经医学杂志》2017年第2期133-138,共6页Chinese Journal of Neuromedicine

基　　金：山东省医药卫生科技发展计划项目（2015WS0352）;青岛市卫生科技计划项目（2015-WJZD091）;青岛市医药科研指导计划项目（2016-WJZD084）

摘　　要：目的探讨丰富环境干预对缺氧缺血性脑损伤（HIBD）幼鼠空间记忆能力及海马区磷酸化环磷腺苷反应元件结合蛋白（pCREB）、凋亡调控基因（Bcl-2、Bax）表达的影响。方法参考相关文献构建标准环境及丰富环境这2种饲养环境。将7d龄Wistar大鼠32只按随机数字表法分为假手术组（n=10）、标准环境组（n=11）、丰富环境组m=11），其中标准环境组及丰富环境组采用改良Rice-Vannucci法制备HIBD模型，假手术组及标准环境组全天置于标准环境饲养．丰富环境组全天置于丰富环境饲养。干预21d后，采用Morris水迷宫定位航行实验检测各组幼鼠寻找隐藏平台的逃避潜伏期，采用Western blotting检测海马区pCREB蛋白表达．采用免疫组化染色检测海马区Bcl-2、Bax表达水平。结果（1）在训练第4、5天，丰富环境组大鼠逃避潜伏期较标准环境组显著缩短，差异均有统计学意义（P〈0．05）。（2）与标准环境组相比，丰富环境组病灶侧海马区pCREB蛋白表达（0．435±0．121 vs0．756±0．101）、Bcl-2表达水平（0．103±0．028vs 0．165±0．017）均显著升高，而Bax表达水平（0．402±0．028vs0．325±0．019）却显著降低，差异均有统计学意义（P＜0．05）。结论HIBD后给予丰富环境干预可显著提高HIBD大鼠的空间记忆能力，CREB-pCREB-凋亡调控基因（Bcl-2、Box）途径可能是丰富环境干预有效性的内在机制之一。Objective To explore the effect of environmental enrichment intervention on spatial memory function, expressions of phosphorylated cAMP response element binding protein （pCREB） and apoptotic regulated genes （Bcl-2 and Box） in the hippocampus of immature rats with hypoxic-ischemic brain damage （HIBD）. Methods Two kinds of raising environments were chosen： standard environment and environmental enrichment. Thirty-two Wistar rats aged 7 days were randomly divided into sham-operated group （n=10）, environmental enrichment group （n=l 1） and standard environment group （n=11）. Rats in both environmental enrichment group and standard environment group were induced animal models of HIBD using the way of Rice-Vannucci. Rats in the sham-operated group and standard environment group were raised in standard environment, while rats in the environmental enrichment group were raised in environmental enrichment. After 21 days of environmental enrichment intervention, the escape latency for searching the hidden platform of immature rats was detected by Morris water maze navigation test. The pCREB protein expression was detected by Western blotting; Bcl-2 and Bax expressions in the hippocampus were detected by immunohistochemisty. Results （1） On the fourth and fifth days of Morris water-maze test, the escape latency in the environmental enrichment group was shorter significantly as compared with that in the standard environment group （P〈0.05）. （2） As compared with the lesion lateral hippocampus of standard environment group, the expressions ofpCREB （0.435±0.121 vs. 0.756±0.101） and Bcl-2 （0.103±0.028 vs. 0.165±0.017） in the lesion lateral hippocampus of environmental enrichment group were significantly higher （P〈0.05）; however, the expression of Bax in the environmental enrichment group was statistically lower （0.402± 0.028 vs. 0.325±0.019, P〈0.05）. Conclusion Environmental enrichment intervention can improve the spatial memory ability in the hippocampus after HIBD, w

关 键 词：缺氧缺血性脑损伤 丰富环境 环磷腺苷反应元件结合蛋白 Bcl-2 BAX 

分 类 号：R742[医药卫生—神经病学与精神病学]