大鼠脑创伤对学习记忆及海马环磷腺苷反应元件结合蛋白的影响

摘要

目的 观察脑创伤早期的脑含水量、环磷腺苷反应元件结合蛋白(CREB)及其磷酸化水平,探讨脑创伤和磷酸化CREB(p-CREB)水平的改变对学习记忆的影响.方法 将54只成年雄性Wistar大鼠,按随机数字表法分为正常组、对照组、创伤性脑损伤(TBI)组,每组18只.采用改良的Feeney法和前期实验参数建立TBI大鼠模型,Western blot观察创伤后12h脑海马组织CREB和p-CREB表达、干湿质量法测定脑组织含水量和Morris水迷宫实验.结果 大鼠TBI后12 h脑组织含水量,与正常组和对照组相比,TBI组升高明显(P＜0.01).与正常组和对照组比较,TBI组大鼠TBI后12h海马CREB和p-CREB蛋白的表达量降低明显;潜伏期增加,2 min内寻求正确次数减少,差异均有统计学意义(P＜0.05).结论 TBI后脑水肿明显,CREB和p-CREB水平降低,可能是使认知和学习记忆功能受损的原因之一.%Objective To observe the change ofbrain water content,levels of cAMP response element binding protein(CREB)and phosphorylated CREB(p-CREB) in the early stage of traumatic brain injury(TBI) and to investigate the effect of TBI and p-CREB on learning and memory.Methods Fifty-four male adult Wistar rats were randomized into the normal group(18 cases),control group(18 cases) and TBI group(18) according to the random number table method.The TBI model was built according to the modified Feeney method and previous experimental parameters.At 12 h after TBI,Western blot analysis were performed to measure the expressions of hippocampal tissue CREB and p-CREB,the Morris water maze test was used to detect the behavior of rats in each group and the wet-dry method was applied to test brain water content.Results The brain water content at 12 h after TBI in the TBI group was remarkably risen compared with the normal group and control group;the expression levels of hippocampal CREB and p-CREB at 12 h after TBI in the TBI group were significantly decreased compared with the normal group and control group,the latent stage was increased and the frequency searching the accuracy within 2 min was decreased.Conclusion Brain edema is obvious after TBI and the levels of CREB and p-CREB are decreased,which maybe one of the reasons for the impairment of learning and memory function after TBI.