长期低剂量氯胺酮对青年早期食蟹猴自发活动和丘脑神经细胞凋亡的影响  

Effects of long-term low-dose ketamine treatment on locomotor activity and apoptosis of thalamus in early adult cynomolgus monkeys

作　　者：张宇哲[1] 江虹[1] 孙琳[1] 李青[1] 孙华[2] 于洪鸾[1] 高进[1] 潘芳[1] 

机构地区：[1]山东大学医学院心理学研究所,济南250012 [2]山东大学附属济南市中心医院急诊科,济南250013

出　　处：《山东大学学报（医学版）》2012年第8期26-30,共5页Journal of Shandong University:Health Sciences

基　　金：香港特别行政区政府禁毒署资助项目(0800-48)

摘　　要：目的探讨氯胺酮长期低剂量给药对食蟹猴自发活动和丘脑细胞凋亡的影响。方法 12只月龄为(46.25±5.40)个月的雄性食蟹猴随机分组为氯胺酮组(8只)和对照组(4只)。氯胺酮组按体质量1 mg/kg每天静脉注射氯胺酮(1 mg/mL),对照组注射相应量的生理盐水(1 mL/kg)。采用观察法定期观察和记录动物给药前后的自发活动。3个月后处死动物,用TUNEL法测丘脑细胞的凋亡状况,Western blot法测得丘脑细胞的Bcl-2和Caspase-3的表达水平。结果实验开始时,对照组和氯胺酮组动物的行走、攀爬、移动和跳跃自发行为无统计学差异。随着用药时间延长,氯胺酮组行为出现了逐渐减少的趋势,至第90天时行走、攀爬、移动和跳跃均低于初次用药时,差异具有统计学意义;对照组自发活动没有明显的改变。这提示氯胺酮组的自发活动行为出现了抑制现象。与对照组相比,氯胺酮组丘脑凋亡细胞增多,丘脑细胞的Caspase-3的表达水平升高,差异都具有统计学意义。Bcl-2的表达水平降低,但差异无统计学意义。结论低剂量氯胺酮持续使用3个月可导致青年早期食蟹猴自发活动显著减少,可能出现了药物耐受现象;低剂量氯胺酮持续应用可致丘脑细胞的凋亡,其机制可能与Caspase-3表达增高有关。Objective To explore effects of long-term low-dose ketamine treatment on locomotor activity and apoptosis of the thalamus in cynomolgus monkeys.Methods 12 male cynomolgus monkeys [（46.25±5.40）months old] were randomly divided into the ketamine group（n=8） and the control group（n=4）.Monkeys in the ketamine group were injected with 1 mg/mL of ketamine,1 mL/kg;while those in the control group were injected with an equal dose of normal saline（1 mL/kg）.Locomotor activities of all monkeys were recorded at regular intervals.3 months later,monkeys were sacrificed.The apoptosis of thalamic cells was observed by TUNEL staining.Western blot was used to detect Caspase-3 and Bcl-2 expressions.Results There was no statistically significant difference in locomotor activity between the ketamine group and the control group.The ketamine group showed a statistically significant decrease in locomotor activity with prolongation of treatment time,while the control group had no statistically significant change.The ketamine group showed a statistically significant increase in apoptosis and the Caspase-3 level in the thalamus compared with the control group.There was no statistically significant difference in the Bcl-2 expression between the two groups.Conclusion Chronic repeated treatment of ketamine with recreational dosage decreases locomotor activities which may be caused by drug tolerance,and induces apoptosis of the thalamus which may be associated with up-regulation of Caspase-3.

关 键 词：氯胺酮 食蟹猴 自发活动 凋亡 青年早期 

分 类 号：R395.1[哲学宗教—心理学]