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| 右美托咪定预处理对创伤后应激障碍小鼠恐惧记忆形成及消退的影响 |
| Effects of dexmedetomidine pretreatment on the formation and extinction of fear memory in post-traumatic stress disorder mice |
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| DOI：10.12089/jca.2022.12.013 |
| 中文关键词: 右美托咪定 预处理 创伤后应激障碍 恐惧记忆 记忆消退 小鼠 |
| 英文关键词: Dexmedetomidine Pretreatment Post-traumatic stress disorder Fear memory Memory extinction Mice |
| 基金项目:国家自然科学基金（81801074，81801081） |
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| 中文摘要: |
目的 观察右美托咪定预处理对创伤后应激障碍（PTSD）小鼠恐惧记忆形成和消退的影响，并探讨其可能的机制。
方法 选择雄性C57/BL6小鼠30只，7～8周龄，体重20～26 g。采用随机数字表法将小鼠分为三组：对照组（C组）、PTSD组（P组）和右美托咪定（D组），每组10只。C组正常饲养，P组和D组通过给予5个成对刺激（声音刺激：30 s，6 000 Hz，85 dB；足底电刺激：声音刺激中最后2 s，1.0 mA）建立PTSD小鼠模型，每个成对刺激间隔20～60 s。C组以及P组在PTSD模型建立前15 min腹腔注射生理盐水1 ml/kg，D组于相同时点腹腔注射右美托咪定20 μg/kg。记录建模前、建模时每个成对刺激时、恐惧记忆获得、消除和再现的僵直时间百分比。采用旷场实验记录运动距离。旷场实验后处死小鼠，采用qPCR法检测海马组织促肾上腺皮质激素受体1（CRHR1）和连接蛋白3（Nectin3）mRNA表达量，采用Western blot法检测CRHR1和Nectin3蛋白含量。
结果 与恐惧记忆消除第1天比较，恐惧记忆消除第2天P组和D组僵直时间百分比明显降低（P<0.05）。与C组比较，P组海马组织CRHR1 mRNA表达量和蛋白含量明显升高，Nectin3 mRNA表达量和蛋白含量明显降低（P<0.05）。与P组比较，D组建模时第4—5个成对刺激时和恐惧记忆再现实验僵直时间百分比明显降低（P＜0.05），海马组织CRHR1 mRNA表达量和蛋白含量明显降低（P<0.05），Nectin3 mRNA表达量和蛋白含量明显升高（P<0.05）。
结论 右美托咪定预处理可以明显减少PTSD小鼠恐惧记忆的形成，并促进恐惧记忆的消退，这可能与CRHR1/Nectin3的表达改变相关。 |
| 英文摘要: |
Objective To observe the effects of dexmedetomidine pretreatment on the formation and extinction of fear memory in post-traumatic stress disorder (PTSD) mice and investigate the possible mechanism.
Methods Thirty male C57/BL6 mice, aged 7-8 weeks, weighting 20-26 g, were randomly divided into three groups: control group (group C), PTSD group (group P) and dexmedetomidine group (group D), 10 mice in each group. Group C was normal feeding, and groups P and D were established PTSD model by giving 5 paired stimuli (sound stimulation: 30 seconds, 6 000 Hz, 85 dB; foot electrical stimulation: the last 2 seconds of sound stimulation, 1.0 mA). The interval time between each paired stimuli was 20-60 seconds. Groups C and P were intraperitoneally injected with saline 1 ml/kg 15 minutes before establishing PTSD model, group D were intraperitoneally injected with dexmedetomidine 20 μg/kg at the same time. The percentage of freezing time before establishing PTSD model, each paired stimuli during the modeling process, fear memory acquisition, elimination and recall were recorded. The open field test was used to determine the activity distance. Mice were sacrificed after the open field test. The qPCR was used to detect the mRNA expression of corticotrophinre receptor 1(CRHR1) and Nectin3 in hippocampus. The Western blot was used to detect the protein expression of CRHR1 and Nectin3.
Results Compared with the first day of fear memory elimination, the percentage of freezing time of groups P and D were significantly decreased on the second day of fear memory elimination (P < 0.05). Compared with group C, CRHR1 mRNA and protein expression in the hippocampus were significantly increased, while Nectin3 mRNA and protein expression in the hippocampus were significantly decreased in group P (P < 0.05). Compared with group P, the percentage of freezing time during the 4th to 5th paired stimuli and fear memory recall experiment were significantly reduced (P < 0.05), CRHR1 mRNA and protein expression in the hippocampus were significantly decreased (P < 0.05), Nectin3 mRNA and protein expression were significantly increased in group D (P < 0.05).
Conclusion Dexmedetomidine pretreatment could significantly reduce the formation of fear memory in PTSD mice, and promote the extinction of fear memory, which might be related with the expression change of CRHR1/Nectin3. |
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