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比较右美托咪定和丙泊酚对小鼠伤害性记忆的影响
The effect of dexmedetomidine and propofol on the nociceptive memory
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DOI:
作者:
唐玲
Tang Ling
作者单位:
上海交通大学医学院附属瑞金医院
Ruijin Hospital,Shanghai Jiao Tong University school of Medicine
关键词:
右美托咪定;丙泊酚;伤害性记忆
Dexmedetomidine;Propofol;Nociceptive Memory
摘要:
[摘要] 目的 研究比较右美托咪定和丙泊酚对小鼠伤害性记忆的作用,探讨可能存在的机制。 方法 将C57BL/6J成年小鼠随机分为3组,右美托咪定组、丙泊酚组和生理盐水组,每组小鼠8~15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24小时和1周测试小鼠的记忆功能,并采用western免疫印迹法检测小鼠杏仁核区cAMP反应元件结合相关蛋白(cAMP-response element bingding protein, CREB)、脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)的表达。 结果 被动躲避训练后24小时和1周测试,各组小鼠进入暗箱的潜伏期较其训练期的基础值显著升高。和丙泊酚及生理盐水组比较,大剂量右美托咪定(200ug/kg)组小鼠在被动躲避训练后24小时进入暗箱的潜伏期明显缩短(右美托咪定组 74±14秒,生理盐水组 186±38秒,丙泊酚组 147±35秒,p<0.05),对小鼠的短期伤害性记忆产生遗忘效应,而被动躲避训练后一周所测定的长期伤害性记忆,两种药物和生理盐水对照组比较均没有显著差异。两种药物处理对小鼠的自主探索行为、运动能力无影响。被动躲避训练后2小时,右美托咪定组的小鼠的杏仁核区CREB磷酸化水平及BDNF含量较丙泊酚组和生理盐水组明显增高。 结论 大剂量右美托咪定影响短期伤害性记忆的巩固;而麻醉剂量丙泊酚对小鼠恐惧反应没有影响。BDNF-CREB通路可能参与了右美托咪定发挥遗忘作用的机制。
[Abstract] Objective To compare the effect between dexmedetomidine and propofol on the nociceptive memory and investigate their mechanisms. Methods Adult C57BL/6 mice were randomly divided into 3 groups (N=8 to 15):dexmedetomidine group, propofol group and control group. Each mouse was trained in the one-trial inhibitory avoidance apparent to form a nociceptive memory, during the consolidation, mice in different groups were treated with different drugs. the retention memory was evaluated 24 hours and 1week after training. The expression of CREB、BDNF in the amygdala was measured by Western blotting. Results The latency was increased significantly after the inhibitory avoidance training in each group. Compared with propofol and saline group, high dose of dexmedetomidine(200ug/kg) has an amnesia effect, it can decreased the latency performance 24 hours after the training (dexmedetomidine group: 74±14s, control group: 186±38s, propofol group: 147±35s, p<0.05) ; One week after the training , no difference among the three groups was observed. There was no significant difference in all groups in open field test. After 2 hours after training, the expressions of p-CREB and BDNF in amygdala of mice in high dose dexmedetomidine group were significantly higher than those in the propofol and saline group . Conclusion High dose of dexmedetomidine can interfere the consolidation of short term nociceptive memory; propofol has no effect on the nociceptive memory; dexmedetomidine promotes the expression of BDNF and p-CREB, which may be involved in the mechanism of the amnesia effect.
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