氯胺酮对抑郁大鼠前额叶神经元nNOS活性及CAPON表达的影响  

Effects of ketamine on nNOS activity and CAPON expression in prefrontal lobe of mentally depressed rats

作　　者：沈一维[1] 闵苏[1] 律峰[1] 李炜[1] 黎平[1] 罗洁[1] 陈婧[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》2013年第1期51-54,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（30972831,81271501）;重庆市教育委员会科学技术研究项目（kj090309）

摘　　要：目的评价氯胺酮对抑郁大鼠前额叶神经元神经型一氧化氮合酶（nNOS）活性及其羧基末端PDZ结构的接头蛋白（CAPON）表达的影响。方法健康成年雄性SPF级sD大鼠，2．5～3．0月龄，体重210～260g，采用慢性轻度不可预见性应激法制备抑郁大鼠模型，取模型制备成功的大鼠24只。采用随机数字表法，将其随机分为2组（n=12）：抑郁组（D组）和氯胺酮组（K组）。另取12只大鼠为对照组（C组）。C组和D组腹腔注射生理盐水10ml／kg，K组腹腔注射氯胺酮，10mg／kg，1次／d，连续7d。于给药前和连续7d给药完成后1d采用旷场实验和糖水偏好实验测定抑郁状态，记录大鼠水平运动距离、站立次数及糖水偏好比。实验测试后1d，采用免疫组织化学法检测前额叶神经元nNOS和CAPON表达水平，采用RT-PCR法检测nNOSmRNA、CAPONmRNA的表达水平。结果与C组比较，D组和K组水平运动距离缩短，站立次数减少，糖水偏好比降低，nNOS及其mRNA表达上调，CAPON及其mRNA表达下调（P〈0．05）。与D组比较，K组水平运动距离延长，站立次数增多，糖水偏好比升高，nNOS及其mRNA表达下调，CAPON及其mRNA表达上调（P〈0．05）。结论氯胺酮可能通过促进抑郁大鼠大脑前额叶神经元CAPON的表达，进而抑制nNOS活性来改善大鼠抑郁状态。Objective To investigate the effects of ketamine on neuronal nitric oxide synthase （nNOS） activity and carboxy-terminal PDZ ligand of nNOS （CAPON） expression in the prefrontal lobe of mentally depressed rats. Methods Adult male Sprague-Dawley rats, aged 2.5-3.0 months, weighing 210-260 g, were used in the study. Mental depression was induced by exposing the rats to chronic unpredictable mild stress. Twenty-four animals in which mental depression was successfully induced were randomly divided into 2 groups （n = 12 each）： mental depression group （group D） and ketamine group （group K）. Another 12 rats were chosen and served as control group （group C）. Group K received intraperitoneal ketamine 10 mg/kg once a day for 7 consecutive days, while groups C and D received intraperitoneal normal saline 10 ml/kg instead of ketamine. Sucrose preference test and open field test were performed before administration and at 1 day after the end of administration. The total distance, number of rearing and sucrose preference percentage （SPP） were recorded. The rats were sacrificed 1 day after the last test for determination of the expression of nNOS and CAPON protein （using immuno-histochemistry） and mRNA （by RT-PCR） in the prefrontal lobe. Results Compared with group C, the total distance was shortened, the number of rearing and SPP were significantly decreased, the expression of nNOS protein and mRNA was up-regulated and the expression of CAPON protein and mRNA was down-regulated in groups D and K （ P 〈 0.05）. Compared with group D, the total distance was prolonged, the number of rearing and SPP were significantly in- creased, the expression of nNOS and mRNA was down-regulated and the expression of CAPON protein and mRNA was up-regulated in group K （ P 〈 0.05） . Conclusion Ketamine can improve the depressive state through promoting the expression of CAPON and inhibiting nNOS activity in the prefrontal lobe of mentally depressed rats.

关 键 词：氯胺酮 抑郁症 一氧化氮合酶I型 

分 类 号：R285.5[医药卫生—中药学]