下调PTEN基因对全脑缺血大鼠学习记忆能力和CREB表达的影响  

Effects of PTEN down-regulation on learning and memory abilities and CREB expression in rats with global cerebral ischemia

作　　者：陈力学[1] 熊新[1] 桂蓓[1] 周冀英[1] 

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市神经病学重点实验室,重庆400016

出　　处：《重庆医科大学学报》2011年第6期673-676,共4页Journal of Chongqing Medical University

基　　金：重庆市卫生局医学科研资助项目(编号:2009-2-357);重庆市教委科研资助项目(编号:KJ100316)

摘　　要：目的:探讨下调第10号染色体同源丢失性磷酸酶张力蛋白基因(Phosphatase and tensin homolog deleted on chromosome ten,PTEN)对全脑缺血再灌注大鼠学习记忆能力及转录因子环磷酸腺苷反应元件结合蛋白(cAMP response element-bind-ing protein,CREB)的表达调控作用。方法:采用海马局部注射pshRNApten基因质粒,建立SD大鼠全脑缺血再灌注模型,利用体感诱发电位(Somatosensory evoked potential,SEP)和穿梭箱分别检查大鼠功能和行为学变化,RT-PCR和免疫组化检测海马神经元CREB mRNA和蛋白的表达。结果:穿梭箱实验发现pshRNApten各治疗组主动回避反应(Active avoiding reaction,AAR)习得率较pshGFP组明显提高;SEP检查显示,pshRNApten组较pshGFP组波幅明显上升,峰潜伏时缩短;pshRNApten组海马神经元CREB基因的mRNA和蛋白表达量较对照组明显上升;以上结果差异均具有统计学意义(P<0.05)。结论:下调PTEN基因能增强全脑缺血再灌注大鼠学习记忆能力,其机制可能与下调PTEN引起CREB表达量增加有关。Objective：To investigate the effects of PTEN down-regulation on learning and memory abilities after global cerebral ischemia in rats.Methods：The experimental therapy model after global cerebral ischemia and reperfusion was established by four-vessel occlusion（4VO）after 2 days of pshRNApten injected into the hippocampal cell layer of SD rats.The behavioral effects were measured with somatosensory evoked potential（SEP）and computerized shuttle-training case respectively.The expression of CREB was analyzed by RT-PCR and immunohistochemistry method.Results：Compared with the pshGFP group,the AAR（active avoiding reaction）with computerized shuttle-training case in the pshRNApten group raise markedly in the first and second week.Results of somatosensory evoked potential（SEP）in pshRNApten group showed that the latency period of P1 wave shorten markedly and P1-N1 amplitude increase significantly after ischemia and reperfusion（P〈0.05）.The expression of rat hippocampal CREB with immunohistoch-emieal method and RT-PCR was obviously increased in pshRNApten treatment groups compared to pshGFP groups.Conclusion：Downregulating PTEN could enhance learning and memory ability and improve neuronal function,which changes were correlated with the increase of CREB.

关 键 词：第10号染色体同源丢失性磷酸酶张力蛋白基因 全脑缺血 体感诱发电位 穿梭箱 转录因子环磷酸腺苷反应元件结合蛋白 

分 类 号：R743.3[医药卫生—神经病学与精神病学]