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

发布时间：2019-06-10 05:00

【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。
[Abstract]:Objective to investigate the effects of long-term low dose ketamine administration on spontaneous activity and apoptosis of thalamus cells in cynomolgus monkeys. Methods Twelve male cynomolgus monkeys aged (46.25 卤5.40) months were randomly divided into ketamine group (n = 8) and control group (n = 4). Ketamine group was injected intravenously with ketamine (1 mg/mL) every day according to body mass of 1 mg/kg, while control group was injected with corresponding amount of saline (1 mL/kg). The spontaneous activities of the animals before and after administration were observed and recorded regularly by observation method. Three months later, the animals were killed, and the apoptosis of thalamic cells was measured by TUNEL method. The expression of Bcl-2 and Caspase-3 in thalamic cells was measured by, Western blot method. Results at the beginning of the experiment, there was no significant difference in the spontaneous behavior of walking, climbing, moving and jumping between the control group and the ketamine group. With the prolongation of medication time, the behavior of ketamine group decreased gradually, and the behavior of ketamine group was lower than that of the first medication on the 90th day, and the difference was statistically significant, but there was no significant change in the spontaneous activity of the control group. This suggests that the spontaneous activity of ketamine group is inhibited. Compared with the control group, the number of apoptotic cells in thalamus and the expression of Caspase-3 in thalamus cells in ketamine group were significantly higher than those in control group, but the expression level of Bcl-2 was lower than that in control group, but the difference was not statistically significant. Conclusion the continuous use of low dose ketamine for 3 months can lead to a significant decrease in spontaneous activity in young cynomolgus monkeys, which may lead to drug tolerance. Continuous application of low dose ketamine can induce apoptosis of thalamic cells, and its mechanism may be related to the increased expression of Caspase-3.
【作者单位】：山东大学医学院心理学研究所;山东大学附属济南市中心医院急诊科;
【基金】：香港特别行政区政府禁毒署资助项目(0800-48)
【分类号】：R96

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