抑郁症模型大鼠海马区磷酸化环磷腺苷反应元件结合蛋白1表达水平及神经元和突触超微结构的研究  

Phospho cAMP response element-binding protein 1 expression level and the ultrastructure of neuron and synapse in hippocampus of depression rats

作　　者：胡茂林[1] 宗小芬 梁炜[2] 张红梅[2] 陈佐明[2] 

机构地区：[1] 中南大学湘雅二医院精神卫生研究所 [2]新乡医学院第二附属医院临床心理科,453002

出　　处：《中华精神科杂志》2015年第2期92-97,共6页Chinese Journal of Psychiatry

基　　金：新乡医学院省级重点学科开放课题（ZD200979）

摘　　要：目的 探讨抑郁症模型大鼠海马区磷酸化环磷腺苷反应元件结合蛋白1（phospho cAMP response element-binding protein 1,p-CREB1）的表达变化对相应神经元、突触超微结构的影响及文拉法辛对p-CREB1表达及神经元、突触超微结构的作用.方法 采用随机数字表法将54只大鼠随机分为正常组（n=12）、抑郁症模型对照组（简称对照组,n=14）、抑郁症模型＋生理盐水组（简称生理盐水组,n =14）和抑郁症模型＋文拉法辛药物干预组（简称药物干预组,n=14）.通过蔗糖水消耗实验、旷场实验检测动物的行为学表现,Morris水迷宫检测学习记忆能力.免疫组织化学检测海马区p-CREB1蛋白表达水平,RT-PCR检测CREB1 mRNA表达水平,透射电子显微镜观察海马区神经元、突触超微结构.p-CREB1阳性细胞数目与Morris水迷宫、突触形态学参数进行相关分析.结果 （1）行为学结果：对照组和生理盐水组蔗糖水消耗分别为（7.4±1.0）、（7.5±1.0） ml/100 g,低于正常组[（9.6±0.3） ml/100g]及药物干预组[（9.4±0.8）ml/100 g;F=17.851,P＜0.01）];Morris水迷宫定位航行实验逃避潜伏期分别为（61.1±10.5）、（59.0±10.6）s,大于正常组[（29.8±10.1）s]及药物干预组[（35.0±8.5）s;F =30.559,P＜0.01].（2）免疫组织化学结果：对照组和生理盐水组大鼠海马p-CREB1阳性细胞数分别为21.07±5.99和24.57±6.97,低于正常组（29.70 ±6.21）及药物干预组（41.50±11.95,F=16.497,P＜0.01）.（3）RT-PCR结果：对照组和生理盐水组大鼠海马CREB1 mRNA吸光度比值分别为0.58±0.47和0.45±0.24,低于正常组（1.03±0.89）及药物干预组（1.10±0.45;F=6.669,P＜0.01）.（4）电镜结果：抑郁症模型大鼠海马神经元和突触超微结构存在病理性改变,药物干预可使其改善.（5） p-CREB1阳性细胞数目与Morris水迷宫、突触形态学参数相关.结论 p-CREB1表达与神经元、突触可塑性有关,文拉法辛可能是�Objective To explore the alterations of ultrastructure of neuron and synapse in rat hippocampus induced by the expression changes of phospho cAMP response element-binding protein 1 （p-CREB1）,and the effect of venlafaxine on the expression of p-CREB1 and relative neuronal and synaptic plasticity.Methods Fifty-four rats were randomly divided into 4 groups：normal group （n =12）,depression model matched group （n =14）,saline group （n =14）,and venlafaxine medication group （n =14）.Sucrose water consumption test and open field test were performed to observe the behavior of animals.To investigate the learning and memory ability,rats were tested by Morris water maze.The expression of p-CREB1 protein was detected by immunohistochemistry and the CREB1 mRNA was measured by RT-PCR.The ultrastructure of neuron and synapse were observed with electron microscope.Correlation analysis was used to measure the associations among the number of p-CREB1 positive cells,the parameters of Morris water maze and synaptic morphology.Results （1） The sucrose consumption in depression model matched group （7.4 ± 1.0） ml/100 g and saline group （7.5 ± 1.0） ml/100 g were significantly less than that in normal group （9.6 ± 0.3） ml/100 g and medication group （9.4 ± 0.8） ml/100 g,（F =17.851,P 〈 0.01）.Morris water maze showed that the escape latent period in depression model matched group （61.1 ± 10.5） s and saline group （59.0 ± 10.6） s were more than that in normal group （29.8 ± 10.1） s and medication group （（35.0 ± 8.5） s;F =30.559,P 〈 0.01）,which demonstrated the learning and memory ability of depression rats were decreased.（2） The positive cell number of p-CREB1 in the hippocampus of depression model matched group （21.07 ±5.99） and saline group （24.57 ±6.97） were lower than that in normal group （29.70 ± 6.21） and medication group （41.50 ± 11.95;F =16.497,P 〈 0.01）.（3） The CREB1 mRNA expression in the hippocampus of depression model matched grou

关 键 词：抑郁症 环磷腺苷反应元件结合蛋白 神经元可塑性 海马 

分 类 号：R749.4[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]