丙泊酚对大鼠海马cAMP效应元件结合蛋白磷酸化和cAMP效应元件结合蛋白mRNA表达水平的影响  

Effects of propofol on cyclic AMP response element binding protein phosphorylation and cyclic AMP response element binding protein mRNA expression in hippocampus of rats

作　　者：张英[1] 吴新海[1] 郑利民[1] 

机构地区：[1]北京大学深圳医院麻醉科,518036

出　　处：《国际麻醉学与复苏杂志》2011年第3期303-307,共5页International Journal of Anesthesiology and Resuscitation

基　　金：深圳市科技局计划项目

摘　　要：目的 探讨丙泊酚对大鼠海马cAMP效应元件结合蛋白（cAMP response element binding protein，CREB）磷酸化和CREB mRNA 表达水平的影响。方法 成年雄性SD大鼠64只，体重250g-280g，采用RandAl．0随机分组软件将实验动物随机分为2组（每组32只），丙泊酚组（P组）于训练前15min腹腔注射丙泊酚9mg／kg，容量2ml／kg；生理盐水组（S组）注射等容量生理盐水。采用避暗箱实验测试大鼠认知功能。首先对大鼠进行训练，记录100S内大鼠不再钻入暗室所需的训练次数。于训练结束后1、3、24h（T1-3）时点记录大鼠在明室停留的时问即记忆潜伏期。各组于给药后15min（To）和T1-3记忆能力测试结束后，各断头处死8只大鼠，分离海马，测定CREB、磷酸化CREB（p-CREB）、CREB mRNA的表达水平。结果 P组大鼠不再钻入暗室所需的训练次数3（1．25）较S组1（0．25）明显增加（P〈0．01）。S组大鼠T1-3时记忆潜伏期均长于300S，P组大鼠T1时潜伏期319（144）s，T2时潜伏期131（114）s，T3时潜伏期56（30）s，提示腹腔注射丙泊酚9mg／kg明显降低大鼠学习获得能力，缩短恐惧记忆的存储时间而发生顺行性遗忘；与S组比较，T0-3时CREB磷酸化水平降低（P〈0．01），T3时海马CREBmRNA表达水平显著降低（P〈0．01），各时点海马CREB的表达差异均无统计学意义（P〈O．05），提示丙泊酚遗忘作用与抑制大鼠海马CREB磷酸化水平、下调CREB mRNA的表达有关。结论 丙泊酚可抑制大鼠海马CREB的磷酸化水平，并下调CREB mRNA的表达水平。Objective to investigate the effects of propofol on cyclic AMP response element binding protein （CREB） phosphorylation and CREB mRNA expression in hippocampus of rats. Methods Sixty-four male Sprague-Dawley （SD） rats weighting 250 g-280 g were randomly divided into 2 groups （n=32） with Randomization Adviser 1.0 software： normal saline treated （Group S） and propofol treated （Group P）. Animals of both groups underwent a continuous multiple-trial inhibitory avoidance training. The times of trial needed for each animal to attain the learning criterion（ 100 seconds） were recorded. Each animal was given intraperitoneal propofol 9 mg/kg or normal saline 2 ml/kg at 15 rain before training. The memory retention was tested at 1, 3 and 24 h（n=8, at each time point） after the training session and the memory latency was recorded. Animals were sacrificed at 15 min after reagent administration （To） and after the memory testing （T1-3）. Hippocampus was obtained to determine the pbosphorylation of CREB （p- CREB） and CREB mRNA expression. Results The times of trials required for the rats to learn the task in Group S and Group P is 1 （0.25） and 3 （1.25）, respectively. Learning ability was significantly impaired in rats of Group P（P〈0.01 ）. Rats of Group S had a median retention latency more than 300 s at each memory testing. The median retention latency of rats in Group P at T1, T2 and T3 was 319（144） s, 131 （114） s and 56（30） s, respectively. Compared with group S, there was a decrease of CREB phosphorylation expression at T0-3 in Group P （P〈O.01）. The CREB mRNA expression in Group P was decreased at T3 （P〈0.01）. Conclusion Propofol can inhibit CREB phosphorylation, and downregulate CREB mRNA expression in hippocampus of rats.

关 键 词：丙泊酚 DNA结合蛋白 cAMP反应元件 海马 

分 类 号：R965[医药卫生—药理学]