下调PTEN对血管性痴呆大鼠海马神经元CREB的调节作用  

The effect of PTEN down-regulation on the expression of CREB in hippocampus of vascular dementia rats

作　　者：韦永琼[1] 陈力学[1] 周冀英[1] 曾照芳[2] 申崇标[2] 黄道超[3] 崔智威[2] 

机构地区：[1]重庆医科大学附属第一医院实验研究中心,重庆400016 [2]重庆医科大学医学检验系 [3]重庆医科大学附属儿童医院动物实验室

出　　处：《中国老年学杂志》2010年第24期3720-3723,共4页Chinese Journal of Gerontology

基　　金：重庆市卫生局医学科研资助项目(2009-2-357);重庆市科委自然科学基金资助项目(编号:CSTC,2007BB5287)

摘　　要：目的探讨PTEN基因对血管性痴呆大鼠海马神经元CREB表达的影响机制。方法 30只大鼠随机分为正常组、AdR-siPTEN干预组、AdRFP阴性对照组,海马CA1区局部注射AdR-siPTEN腺病毒后2 d,采用双侧颈总动脉永久性结扎(2-VO)法建立血管性痴呆模型,4 w后应用HE染色检测神经元的损伤,RT-PCR和免疫组织化学检测CA1区Akt、CREB mRNA的表达。结果海马部位有PTEN基因红色荧光蛋白表达,并有PTEN基因的mRNA表达量明显下降(P<0.01);HE染色显示,AdR-siPTEN组海马神经元损伤和变性程度明显轻于AdRFP阴性对照组大鼠;RT-PCR和免疫组化染色结果显示,与AdRFP组相比,AdR-siPTEN治疗组CA1区Akt、CREB的mRNA和蛋白表达水平显著升高(P<0.05)。结论下调PTEN基因可通过Akt增加CREB的表达,从而改善血管性痴呆大鼠神经元突触可塑性,达到减轻神经元损伤、提高学习记忆和神经保护的目的 。Objective To investigate the regulation of PTEN on the expression of CREB protein in hippocampus of vascular dementia（VD） rats,and provide a theoretical foundation for the study of VD synaptic plasticity.Methods In VD model with permanent bilateral common carotid artery ligation（2-VO）,AdR-siPTEN recombinant adenovirus and unrelated control adenovirus AdRFP were injected into VD rat hippocampus respectively.After 4 weeks,HE staining was used to detect the neuronal damage in the hippocampus CA1 region,and the expressions of Akt and CREB were detected by RT-PCR and immunohistochemistry and analyzed by image analysis system.Results There was definite expression of Akt/CREB in CA1 region of hippocampus in normal group,while it was less in AdRFP negative control group than that in normal group and more in AdR-siPTEN treatment group than that in AdRFP group（P0.01）.Conclusions PTEN down-regulation could effectively regulate the expression of CREB through Akt,and participate in the protective effect of neuronal synaptic plasticity in VD rat.

关 键 词：第10号染色体同源丢失性磷酸酶张力蛋白基因 血管性痴呆 转录因子环磷酸腺苷反应元件结合蛋白 突触可塑性 

分 类 号：R749.1[医药卫生—神经病学与精神病学]