右美托咪定预防大鼠创伤后应激障碍的效果及其对海马ERK活性及ARC表达的影响  

Efficacy of dexmedetomidine in prevention of posttraumatic stress disorder and effects of dexmedetomidine on ERK activity and ARC expression in hippocampus in rats

作　　者：张瑶[1] 孙茜[1] 许倩[1] 舒银银[1] 李永乐[1] 刘清珍[1] 刘健[1] 李伟彦[1] 

机构地区：[1]南方医科大学南京临床医学院南京军区南京总医院麻醉科,210002

出　　处：《中华麻醉学杂志》2013年第2期242-244,共3页Chinese Journal of Anesthesiology

基　　金：南京军区医药卫生科研基金（11MA090）

摘　　要：目的评价右美托咪定预防大鼠创伤后应激障碍（PTSD）的效果及其对海马细胞外信号调节激酶（ERK）活性及活动调节骨架蛋白（ARC）表达的影响。方法成年雄性sD大鼠68只，体重250-280g，采用随机数字表法，将大鼠分为4组（n=17）：生理盐水组（Ns组）、右美托咪定0．3μg／kg组（D1组）、右美托咪定3．0μg／kg组（D2组）和右美托咪定9．0μg／kg组（D，组）。于PTSD模型制备前30min，NS组腹腔注射生理盐水2ml，D1、D2组和D3分别腹腔注射右美托咪定0．3、3．0和9．0μg／kg。采用应激增强恐惧学习法制备PTSD模型。于模型制备第1天A室电击处理后15min时采用Westernblot法检测海马ERK、磷酸化ERK（p-ERK）的表达水平；第1天A室电击处理后30rnin时采用Westernblot法检测海马ARC的表达水平。结果与模型制备第2天比较，3组大鼠模型制备第3天木僵率升高（P〈0．05）；与NS组比较，D2组和D2组模型制备第3天木僵率均下降，海马p-ERK和ARC表达降低（P〈0．05），D1组上述指标差异无统计学意义（P〉0，05）；D2组和D3组上述指标比较差异无统计学意义（P〉0．05）。4组大鼠海马ERK表达差异无统计学意义（P〉0．05）。结论右美托咪定对大鼠PTSD有一定预防作用，且与剂量有关，该作用机制与抑制海马ERK活性，下调ARC表达有关。Objective To evaluate the efficacy of dexmedetomidine in prevention of posttraumatic stress disorder （PTSD） and effects of dexmedetomidine on extracellular signal-regulated kinase （ERK） activity and activ- ity-regulated-cytoskeletal protein （ARC） expression in hippocampus in rats. Methods Sixty-eight adult male Spra- .gue-Dawley rats, weighing 250-280 g, were randomly divided into 4 groups （ n = 17 each） ： normal saline group （group NS） and dexmedetomidine 0.3, 3.0 and 9.0 μg/kg groups （groups D1 , D2, D3 ）. An animal model of PTSD, stress-enhanced fear learning （lasting for 3 days）, was made. In group NS normal saline 2 ml was injected intraperitioneally at 30 min before stress-enhanced fear learning, while in groups D1 , D2 and D3, dexmedetomidine 0.3, 3.0 and 9.0 μg/kg were injected intraperitioneally, respectively, at 30 rain befbre stress-enhanced fear learn- ing. The expression of ERK and phosphorylated ERK （p-ERK） in hippocampus was measured by Western blot at 15 min after exposure to electrical shocks in one environment （Context A） on 1 st day the model was established. The expression of ARC in hippocampus was detected by Western blot at 30 min after exposure to electrical shocks in Context A on 1 st day the model was established. Results The freezing rate was significantly higher on 3rd daythan on 2nd day in each group （ P 〈 0.05）. Compared with group NS, the freezing rate was significantly decreased and the expression of p-ERK and ARC was down-regulated on 3rd day in groups D1 and D3 （P 〈 0.05）, and no significant change was found in the parameters mentioned above in group D1 （ P 〉 0.05）. There was no significant difference in the paramenters mentioned above between groups D2 and D3 （ P 〉 0.05 ）. There was no significant dif- ference in the expression of ERK between the four groups （ P 〉 0.05 ）. Conclusion Dexmedetomidine prevents PTSD to some extent in a dose-dependent manner and inhibition of ERK activity and decrease in ARC express

关 键 词：右美托咪啶 应激障碍 创伤后 细胞外信号调节MAP激酶类 细胞支架蛋白质类 

分 类 号：R614[医药卫生—麻醉学]