咪达唑仑对大鼠海马ERK1、ERK2和CREB磷酸化水平的影响  

Effects of midazolam on ERK1, ERK2 and CREB phosphorylation in hippocampal in rats

作　　者：张英[1] 吴新民[1] 

机构地区：[1]北京大学第一医院麻醉科,100034

出　　处：《中华麻醉学杂志》2009年第5期439-442,共4页Chinese Journal of Anesthesiology

摘　　要：目的探讨咪达唑仑对大鼠海马细胞外信号调节激酶1（ERK1）、ERK2和cAMP反应元件结合蛋白（CREB）磷酸化水平的影响。方法成年雄性SD大鼠80只，体重250—300g，随机分为2组（n=40）：对照组（C组）和眯达唑仑组（M组）。采用避暗法测试大鼠认知功能。首先对大鼠进行训练，记录100s内大鼠不再钻人暗室所需的训练次数。训练前15min时M组腹腔注射咪达唑仑3mg／kg（用生理盐水稀释至2ml／kg），C组注射等容量生理盐水。于训练结束后30min、1、2、24h（T1-4）时，记录大鼠在明室停留的时间，即记忆潜伏期。各组于给药后15min（T0）和T1-4认知功能测试结束后，各处死8只大鼠，分离海马，测定ERK1、ERK2和CREB的磷酸化水平。结果与C组比较，M组大鼠不再钻入暗室所需的训练次数增加，T2-4时记忆潜伏期缩短，T0.3-4时ERK1磷酸化水平降低，T0-4时ERK2和CREB的磷酸化水平降低（P〈0．01）。结论咪达唑仑可抑制大鼠海马ERK1、ERK2和CREB的磷酸化。Objective To investigate the effects of midazolam on extracellular signal-regulated kinase 1 （ERK1）, ERK2 and cyclic AMP response element binding protein （CREB） phosphorylation in hippocampal in rats. Methods Eighty male SD rats weighing 250-300 g were randomly divided into 2 groups （ n = 40） ： group control （group C） and group midazolam （group M）. The animals underwent a continuous multi-trial inhibitory avoidance training. The times of trial needed for each animal to attain the learning criterion （100 s） were recorded. Each animal was given intraperitoneal midazolam 3 mg/kg or normal saline 2 ml/kg at 15 min before training. The memory retention was tested at 0.5,1,2 and 24 h （n = 8,at each time point）after the training session and the memory latency was recorded.The animals were sacrificed 15 min after administration （To ） and after the memory testing （T1-4） and hippocampus was obtained for determination of phosphorylated ERK1 （p-ERK1）, p-ERK2 and p-CREB expression. Results Compared with group C, the times of trial to attain the learning criterion were significantly increased, memory latency shortened at T2-4, ERK1 phosphorylation decreased at T0.3.4 while ERK2 and CREB phosphorylation decreased at T0.4. Conclusion Midazolam can inhibit ERK1, ERK2 and CREB phosphorytation in hippocampal in rats.

关 键 词：咪达唑仑 细胞外信号调节MAP激酶类 DNA结合蛋白 环AMP反应性 海马 

分 类 号：R96[医药卫生—药理学]