中华精神科杂志
中華精神科雜誌
중화정신과잡지
CHINESE JOURNA OF PSYCHIATRY
2015年
2期
92-97
,共6页
胡茂林%宗小芬%梁炜%张红梅%陈佐明
鬍茂林%宗小芬%樑煒%張紅梅%陳佐明
호무림%종소분%량위%장홍매%진좌명
抑郁症%环磷腺苷反应元件结合蛋白%神经元可塑性%海马
抑鬱癥%環燐腺苷反應元件結閤蛋白%神經元可塑性%海馬
억욱증%배린선감반응원건결합단백%신경원가소성%해마
Depressive disorder%Cyclic AMP response element-binding protein%Neuronal plasticity%Hippocampus
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,文拉法辛可能是通过影响p-CREB1表达和神经元、突触可塑性来发挥治疗作用.
目的 探討抑鬱癥模型大鼠海馬區燐痠化環燐腺苷反應元件結閤蛋白1(phospho cAMP response element-binding protein 1,p-CREB1)的錶達變化對相應神經元、突觸超微結構的影響及文拉法辛對p-CREB1錶達及神經元、突觸超微結構的作用.方法 採用隨機數字錶法將54隻大鼠隨機分為正常組(n=12)、抑鬱癥模型對照組(簡稱對照組,n=14)、抑鬱癥模型+生理鹽水組(簡稱生理鹽水組,n =14)和抑鬱癥模型+文拉法辛藥物榦預組(簡稱藥物榦預組,n=14).通過蔗糖水消耗實驗、曠場實驗檢測動物的行為學錶現,Morris水迷宮檢測學習記憶能力.免疫組織化學檢測海馬區p-CREB1蛋白錶達水平,RT-PCR檢測CREB1 mRNA錶達水平,透射電子顯微鏡觀察海馬區神經元、突觸超微結構.p-CREB1暘性細胞數目與Morris水迷宮、突觸形態學參數進行相關分析.結果 (1)行為學結果:對照組和生理鹽水組蔗糖水消耗分彆為(7.4±1.0)、(7.5±1.0) ml/100 g,低于正常組[(9.6±0.3) ml/100g]及藥物榦預組[(9.4±0.8)ml/100 g;F=17.851,P＜0.01)];Morris水迷宮定位航行實驗逃避潛伏期分彆為(61.1±10.5)、(59.0±10.6)s,大于正常組[(29.8±10.1)s]及藥物榦預組[(35.0±8.5)s;F =30.559,P＜0.01].(2)免疫組織化學結果:對照組和生理鹽水組大鼠海馬p-CREB1暘性細胞數分彆為21.07±5.99和24.57±6.97,低于正常組(29.70 ±6.21)及藥物榦預組(41.50±11.95,F=16.497,P＜0.01).(3)RT-PCR結果:對照組和生理鹽水組大鼠海馬CREB1 mRNA吸光度比值分彆為0.58±0.47和0.45±0.24,低于正常組(1.03±0.89)及藥物榦預組(1.10±0.45;F=6.669,P＜0.01).(4)電鏡結果:抑鬱癥模型大鼠海馬神經元和突觸超微結構存在病理性改變,藥物榦預可使其改善.(5) p-CREB1暘性細胞數目與Morris水迷宮、突觸形態學參數相關.結論 p-CREB1錶達與神經元、突觸可塑性有關,文拉法辛可能是通過影響p-CREB1錶達和神經元、突觸可塑性來髮揮治療作用.
목적 탐토억욱증모형대서해마구린산화배린선감반응원건결합단백1(phospho cAMP response element-binding protein 1,p-CREB1)적표체변화대상응신경원、돌촉초미결구적영향급문랍법신대p-CREB1표체급신경원、돌촉초미결구적작용.방법 채용수궤수자표법장54지대서수궤분위정상조(n=12)、억욱증모형대조조(간칭대조조,n=14)、억욱증모형+생리염수조(간칭생리염수조,n =14)화억욱증모형+문랍법신약물간예조(간칭약물간예조,n=14).통과자당수소모실험、광장실험검측동물적행위학표현,Morris수미궁검측학습기억능력.면역조직화학검측해마구p-CREB1단백표체수평,RT-PCR검측CREB1 mRNA표체수평,투사전자현미경관찰해마구신경원、돌촉초미결구.p-CREB1양성세포수목여Morris수미궁、돌촉형태학삼수진행상관분석.결과 (1)행위학결과:대조조화생리염수조자당수소모분별위(7.4±1.0)、(7.5±1.0) ml/100 g,저우정상조[(9.6±0.3) ml/100g]급약물간예조[(9.4±0.8)ml/100 g;F=17.851,P＜0.01)];Morris수미궁정위항행실험도피잠복기분별위(61.1±10.5)、(59.0±10.6)s,대우정상조[(29.8±10.1)s]급약물간예조[(35.0±8.5)s;F =30.559,P＜0.01].(2)면역조직화학결과:대조조화생리염수조대서해마p-CREB1양성세포수분별위21.07±5.99화24.57±6.97,저우정상조(29.70 ±6.21)급약물간예조(41.50±11.95,F=16.497,P＜0.01).(3)RT-PCR결과:대조조화생리염수조대서해마CREB1 mRNA흡광도비치분별위0.58±0.47화0.45±0.24,저우정상조(1.03±0.89)급약물간예조(1.10±0.45;F=6.669,P＜0.01).(4)전경결과:억욱증모형대서해마신경원화돌촉초미결구존재병이성개변,약물간예가사기개선.(5) p-CREB1양성세포수목여Morris수미궁、돌촉형태학삼수상관.결론 p-CREB1표체여신경원、돌촉가소성유관,문랍법신가능시통과영향p-CREB1표체화신경원、돌촉가소성래발휘치료작용.
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 group (0.58 ± 0.47) and saline group (0.45 ± 0.24) were less than that in normal group (1.03 ± 0.89) and medication group (1.10 ± 0.45;F =6.669,P ＜ 0.01).(4) There were pathologic alterations in the ultrastructure of neurons and synapses in the hippocampus of depression rats,which were improved by pharmacological intervention.(5) The number of p-CREB1 positive cells was related to the parameters of Morris water maze and synaptic morphology.Conclusion p-CREB1 expression is correlated with neuronal and synaptic plasticity,and venlafaxine may be effective through influencing the expression of p-CREB1 and neuronal and synaptic plasticity.
