氯胺酮在点燃模型作用中的量效关系

Dosage-dependent effect of ketamine on kindled models

目的:观察氯胺酮对大鼠杏仁核电刺激点燃和化学性点燃模型的作用,并了解其是否有量效关系。方法:实验在青岛大学医学院药理学研究室进行。①杏仁核电刺激点燃模型制备:用恒定电流刺激Wistar雌鼠右侧杏仁核(400μA单相方波,波宽1ms,频率60Hz,持续1s,1次/d),若动物连续3次出现RacinesⅤ级发作反应(全身痉挛、强直惊厥)即被完全点燃。②取点燃大鼠24只随机分为3组(n=8),分别腹腔注射氯胺酮30.0,10.0,5.0mg/kg,30min后测定后放电阈值,记录在后放电阈值刺激下的后放电时程和Racines分级。③取点燃大鼠24只随机分为3组(n=8),分别腹腔注射氯胺酮5.0mg/kg,尼卡地平2mg/kg,氯胺酮5.0mg/kg合并尼卡地平2mg/kg,记录给药前后后放电时程以及Racines分级。④腹腔注射盐酸利多卡因40mg/kg制备大鼠利多卡因化学点燃模型,取点燃大鼠28只随机分为4组(n=7),分别腹腔注射氯胺酮5.0,10.0,20.0,30.0mg/kg,30min后腹腔注射利多卡因40mg/kg,测定1h内大鼠发作Racines分级,计算给药前后V级发生百分率。结果:76只大鼠进入结果分析。①氯胺酮对大鼠杏仁核点燃发作影响:氯胺酮10.0,30.0mg/kg组大鼠给药后后放电时程显著短于给药前(P<0.05),Racines发作级别显著低于给药前(P<0.01)。②氯胺酮5.0mg/kg和尼卡地平2.0mg/kg合用能缩短点燃大鼠的后放电时程[(42.3±9.7),(60.6±10.3)s,P<0.05],降低Racines发作级别(3.1±0.7,5.0±0,P<0.05)。③腹腔注射氯胺酮20.0,30.0mg/kg可降低大鼠利多卡因化学点燃模型的V级发作百分率(50.0%,100%;12.5%,100%)。结论:氯胺酮对大鼠杏仁核点燃和利多卡因化学点燃模型具有抑制作用,与尼卡地平有协同作用,并有显著的量效关系。

AIM：To observe the role of ketamine on amygdala kindling and chemical kindling models in rats,and investigate whether there is a dosagedependent effect. METHODS：The experiment was carried out in the Department of Pharmacology, Medical College of Qingdao University. （1） Establishment of amygdala kindling models in rats：The rats received the kindling stimulus once a day,which consisted of a 1 s train of 60 Hz, 400μA,A and monophasic square wave pulses at the intensity described below.Animals which displayed 3 consecutive seizures on stage 5 were defined as kindled.（2） The kindled rats were given intraperitoneal injection of ketamine（30.0, 10.0 and 5.0 mg/kg, n=8）. Thirty minutes after administration the ADD and Racine＇s stage of the ketamine on amygdala kindling models were recorded. The rats were previously given the same volume of saline as control.（3） Intraperitoneal injection of ketamine （5.0 mg/kg,n=8）,nicardipine（2.0 mg/kg, n=8）, ketamine （5.0 mg/kg） combined with nicardipine （2.0 mg/kg） （n=8） were performed, and Racine＇s stage were recorded according to the evaluation criterion.（4） Twenty-eight rats were randomly divided into 3 groups with 8 rats in each group. Lidocaine-induced （lidoeaine, 40 mg/kg, intraperitoneal injection） chemical kindled models were performed in rats and the effects of ketamine （5.0, 10.0, 20.0 and 30.0 mg/kg, intraperitoneal injection） were observed after 30 minutes on kindled models,Racine＇s stage were recorded according to the evaluation criterion. RESULTS：Totally 76 rats were involved in the analysis of results. （1） Effect of ketamine on amygdala kindling rats： Ketamine （10.0-30.0 mg/kg） shortened the after discharge duration （P 〈 0.01） and reduced the Racine＇s stage （P 〈 0.05）.（2） The combination of ketamine （5.0 mg/kg） with nicardipine （2.0 mg/kg） shortened the after discharge duration [（42.3±9.7）, （60.6±10.3）s, P 〈 0.05] and reduced Racine＇s stages （3.1±0.7,5.0±0,P〈0.05）.（3） Ketamine （20.0-30.0 mg/kg） significantly reduced the Racine＇s stage and reduced the rate of Racine＇s stage V grade in chemical kindled models induced by lidocaine （50.0%, 100%; 12.5%, 100%）. CONCLUSION：Ketamine dosage-dependently inhibits the seizure of the amygdala kindled and chemical kindled models induced by lidocaine.The combination of ketamine with nicardipine at ineffective dose shortened the after discharge duration and reduced Racine＇s stages.