比较右美托咪定与丙泊酚对小鼠伤害性记忆的影响

Comparison of the effects of dexmedetomidine and propofol on nociceptive memory of mice

目的比较右美托咪定(DEX)与丙泊酚对小鼠伤害性记忆的作用,探讨可能的作用机制。方法将75只C57BL/6J成年小鼠随机分入DEX 50\mg/kg组(DEX50组,10只)、DEX 150\mg/kg组(DEX150组,10只)、DEX 200\mg/kg组(DEX200组,15只)、丙泊酚150mg/kg组(丙泊酚150组,10只)、丙泊酚200mg/kg组(丙泊酚200组,15只)和0.9%氯化钠溶液组(对照组,15只)。采用被动躲避实验建立小鼠的伤害性记忆研究模型,在记忆的巩固期分别给予药物处理,训练后24h和1周测试小鼠的记忆功能。在被动躲避实验训练后48h进行旷场实验,记录小鼠的运动速度、中央区的停留时间、穿越次数和进入中央区的潜伏期。采用Western印迹法检测小鼠杏仁核区cAMP效应元件结合蛋白(CREB)、脑源性神经营养因子(BDNF)的表达。结果 6组小鼠在被动躲避实验训练后24h和1周测试的潜伏期均显著长于同组训练期时(P值均<0.05)。DEX200组训练后24h测试的潜伏期显著短于其余5组同时间(P值均<0.05),其余5组间的差异均无统计学意义(P值均>0.05)。6组间在被动躲避实验训练后1周测试的潜伏期,以及在旷场实验中运动速度、中央区的停留时间、穿越次数和进入中央区的潜伏期的差异均无统计学意义(P值均>0.05)。DEX200组BDNF蛋白相对表达量有高于对照组、丙泊酚200组的趋势,但差异均无统计学意义(P值均>0.05);磷酸化的CREB(p-CREB)的蛋白相对表达量显著高于对照组和丙泊酚200组(P值均<0.05)。结论 200\mg/kg的DEX影响短期伤害性记忆的巩固,而麻醉剂量的丙泊酚对此记忆无影响。大剂量的DEX通过上调BDNF和p-CREB发挥了伤害性记忆的遗忘作用。

Objective To compare the effect of dexmedetomidine （DEX） with propofol on the nociceptive memory and investigate the possible mechanisms. Methods A total of 75 adult 057BL/6 mice were randomly divided into 6 groups： DEX 50 μg/kg （DEX 50） group （n= 10）, DEX 150 μg/kg （DEX 150） group （n= I0）, DEX 200μg/kg （DEX 200） group （n = 15）, propofol 150 mg/kg （propofol 150） group （n = 10）, propofol 200 mg/kg （propofol 200） group （n= 15） and normal saline （control） group （n = 15）. Each mouse received the inhibitory avoidance training to form a nociceptive memory. During the consolidation, mice in different groups were treated with different concentrations of drugs. The retention memory was evaluated 24 hours and 1 week after the training. Open field test was performed to record velocity, center frequency, center times and latency to center 48 h after avoidance training. The expression of cyclic adenosine monophosphate （cAMP） response element bindin （CREB） and brain-derived neurotrophic factor （BDNF） in the amygdala were measured by Western blotting. Results The latency were increased significantly 24 hours and 1 week after the inhibitory avoidance training in each group （all P〈0.05）. Twenty-four hours after avoidance training, the latency in DEX 200 group was significantly decreased as compared with the other 5 groups （all P〈0.05）, while there were no significant difference in the latency between DEX 50 group, DEX 150 group, propofol 150 group, propofol 200 group and control group （all P〈 0.05）. There were no significant differences in the open field test （including velocity, center frequency, centertimes and latency to center） or latency one week after avoidance training between groups （all P〉0. 05）. Compared with that in the control group and propofol 200 group, the expression of BDNF in DEX 200 group was increased, but no significant differences were found （both P 〉 0.05）. The expression of phosphorylated CREB （p-CREB） in DEX 200 group was significantly higher than those in the propofol 200 group and control group （both P〈0.05）. Conclusion Two hundred pg/kg DEX can interfere with the consolidation of short-term nociceptive memory. Propofol has no effect on the nociceptive memory. DEX promotes the expression of BDNF and p-CREB, which may be involved in the mechanism of the amnesia.