反复给予氯胺酮对大鼠海马神经元磷酸化丝切蛋白表达的影响  

Effect of repeated ketamine administration on phosphorylated cofilin in rat hippocampus

作　　者：葛建岭[1] 朋立超[1] 

机构地区：[1]复旦大学附属第五人民医院麻醉科,上海200240

出　　处：《上海医学》2014年第2期135-138,F0003,共5页Shanghai Medical Journal

基　　金：上海市闵行区卫生局科研项目资助(2010MW01)

摘　　要：目的观察反复给予氯胺酮对大鼠海马神经元磷酸化丝切蛋白(p-cofilin)表达的影响,探讨其参与氯胺酮导致认知功能障碍发生的机制。方法将40只2月龄Sprague-Dawley雄性大鼠随机分为氯胺酮组和0.9%氯化钠溶液组(对照组)。氯胺酮组和对照组大鼠每天分别予腹腔内注射氯胺酮(50mg/kg)或等体积的0.9%氯化钠溶液(1mL/kg),连续7d。停止注射氯胺酮2d后应用Morris水迷宫行定位航行实验和空间探索实验,检测两组大鼠的学习记忆能力,并从氯胺酮组中筛选出认知功能障碍大鼠(认知障碍组)。采用Western印迹法检测认知障碍组和对照组大鼠海马内p-cofilin和丝切蛋白(cofilin)的表达量。结果氯胺酮组实验第3、4、5天的逃逸潜伏期均显著长于对照组同时间点(P值均<0.05)。氯胺酮组的穿越平台次数显著少于对照组(P<0.05);平台象限停留时间也显著缩短(P<0.05);两组间游泳速度的差异无统计学意义(P>0.05)。认知障碍组大鼠海马内p-cofilin蛋白表达量显著低于对照组(P<0.05),而两组间cofilin蛋白表达量的差异无统计学意义(P>0.05)。结论反复给予氯胺酮可导致大鼠发生认知功能障碍,且大鼠海马内p-cofilin的蛋白表达量降低。Objective To investigate the effect of repeated ketamine administration on phosphorylated cofilin （p-cofilin） in the hippocampus of rats and the possible mechanism of cognitive dysfunction caused by ketamine. Methods Forty male Sprague-Dawley rats （2 months old） were randomly divided into ketamine group and control group. Ketamine （50 mg/kg） and normal saline （ 1 mL/kg） were intraperitoneally injected for 7 days in the rats of ketamine group and control group, respectively. Morris water maze test was adopted to explore the latency in place navigation and spatial probe ability 2 days after injection, and the rats with cognitive deficit was screened from the ketamine group. The expression of p-cofilin and cofilin in the hippocampus of the cognitive deficit group and control group were detected by Western blot. Results The latency in place navigation of the ketamine group on day 3, 4 and 5 of Morris test were significantly longer than that of the control group （all P〈0.05）. The times of crossing platform in the ketamine group was significantly less than that in the control group （P〈0.05）. Platform quadrant detention time of ketamine group was significantly shorter than that of control group （P〈0.05）. The swimming speed of ketamine group was not statistically different from control group （P 〉 0.05）. The expression level of p-cofilin in the cognitive deficit group was significantly lower than that in the control group （P〈 0.05）, while there was no significant difference in the expression of cofilin between these two groups （P〉0.05）. Conclusion Repeated administration of ketamine in rats may result in cognitive dysfunction and reduce p-cofilin in the hippocampus.

关 键 词：氯胺酮 磷酸化丝切蛋白 丝切蛋白 MORRIS水迷宫 WESTERN印迹法 

分 类 号：R614[医药卫生—麻醉学]