小剂量氯胺酮复合异丙酚麻醉下电休克对抑郁大鼠海马p-GluR1和p-CaMKⅡα表达的影响  

Effect of electroconvuisive therapy on p-GluR1 and p-CaMK Ⅱα expression under small dose ketamine combined with propofol anesthesia in depressed rats

作　　者：秦珮珮 闵苏[1] 罗洁[1] 张帆[1] 朱贤林[1] 郝学超[1] 

机构地区：[1]重庆医科大学附属第一医院麻醉科,400016

出　　处：《中华麻醉学杂志》2016年第2期203-206,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81271501）;国家临床重点专科建设项目[财社（2011）170号];重庆市应用开发计划项目（cstc2014yykfA110028）

摘　　要：目的评价小剂量氯胺酮复合异丙酚麻醉下电休克（ECT）对抑郁大鼠海马磷酸化谷氨酸受体1（p-GluR1）和磷酸化钙／钙调素依赖性蛋白激酶Ⅱα表达（p-CaMKⅡα）的影响。方法清洁级健康成年雄性SD大鼠，体重200～250g，2—3月龄，采用慢性不可预见性轻度应激法建立大鼠抑郁模型。建立模型成功的大鼠40只，采用随机数字表法分为5组（n=8）：M0-4组腹腔注射异丙酚80mg／kg及氯胺酮10mg／kg复合麻醉，待翻正反射消失后行不同电量ECT（频率50Hz、正弦波、脉冲宽度0．7ms、持续1S），1次，d，连续7d。M0组两耳夹电极不通电，M1-4组电量分别为60、120、180和240mC。于建模前、建模后1d、ECT后1d行糖水偏好实验，计算糖水偏好百分比（SPP）。于建模后4d、ECT后4d行Morris水迷宫实验。随后处死大鼠取海马，采用Western blot法检测GluRl、p-GluRl、CaMKⅡα和p-CaMKⅡα／的表达。结果与建模前比较，M0-4组建模后SPP降低（P〈0．05）。与建模后比较，M1-4组ECT后SPP增加，逃避潜伏期缩短，目标象限探索时间延长（P〈0．05）；M。组间ECT后SPP比较差异无统计学意义（P〉0．05）。ECT后，与M0组比较，M1-4组SPP升高，海马p-GluRl及p-CaMKⅡα表达上调（P〈0．05）；与M2组比较，其余组逃避潜伏期延长，目标象限探索时间缩短，海马p-GluRl及p-CaMKⅡα表达下调（P〈0．05）；5组间ECT后海马GluRl和caMKⅡα表达比较差异无统计学意义（P〉0．05）。结论小剂量氯胺酮复合异丙酚麻醉下ECT抗抑郁时可损害大鼠认知功能，其机制与调控CaMKⅡα和GluRl的磷酸化水平有关。Objective To evaluate the effect of electroconvulsive therapy （ECT） on the expression of phosphorylated glutamate receptor 1 （p-GluR1） and Ca2＋/calmodulin-dependent protein kinaseⅡα （p-CaMK Ⅱα） under small dose ketamine combined with propofol anesthesia in the depressed rats. Methods Forty healthy adult male Sprague-Dawley rats, weighing 200-250 g, aged 2-3 months, were used in this study. Mental depression was induced by exposing the animals to chronic unpredictable mild stress （CUMS）. Forty mentally depressed rats were divided randomly into 5 groups （ n = 8 each） using a random number table： M0.4 groups. Propofol 80 mg/kg and ketamine 10 mg/kg were injected intraperitoneally in M0-4 groups. After disappearance of righting reflex, M1-4 groups received ECT of 60, 120, 180 and 240 mC once a day for 7 consecutive days, respectively, by means of a current （frequency 50 Hz, sine-wave, pulse width 0.7 ms, 1-s duration） delivered via ear-clip electrodes, while group M0 received ECT of no quantity of electric charge via ear-clip electrodes. Before CUMS, at I day after CUMS and at 1 day after ECT, sucrose preference test was applied to evaluate the depressive behavior. The sucrose preference percentage （SPP） was calculated. At 4 days after CUMS and 4 days after ECT, the learning and memory function was assessed using Morris water maze test. The rats were then sacrificed, and hippocampi were isolated to detect the expression of GluR1, p-GluR1, CaMK Ⅱα and p-CaMKⅡα by Western blot. Results The SPP was significantly lower after CUMS than before CUMS in M0-4 groups （P〈 0.05）. Compared with that after CUMS, the SPP was significantly increased, the escape latency was shortened, and the space exploration time was prolonged after ECT in M1-4 groups （P〈0.05）. There was no significant difference in SPP after ECT between M1,4 groups （P〉0.05）. Compared with group M0, the SPP was significantly increased, and the expression of pGluR1 and p-CaMK Ⅱα was up-regulated in M1-

关 键 词：氯胺酮 二异丙酚 电休克 抑郁 受体 谷氨酸 蛋白激酶类 

分 类 号：R614[医药卫生—麻醉学]