天津医药

天津医药 ›› 2019, Vol. 47 ›› Issue (3): 250-255.doi: 10.11958/20182121

• 实验研究 • 上一篇    下一篇

右美托咪定减轻新生期大鼠重复七氟醚吸入导致的远期突触可塑性损害

梁小丽，桂欢，刘程曦，张超，徐珊，张益，朱昭琼    

  1. 1遵义医科大学附属医院麻醉科（邮编563000）；2贵州省麻醉与器官保护基础研究重点实验室；3遵义医科大学麻醉医学院
  • 收稿日期:2018-12-26 修回日期:2019-01-21 出版日期:2019-03-15 发布日期:2019-04-24
  • 通讯作者: 朱昭琼 E-mail:zy_ane@yahoo.com

Dexmedetomidine alleviates the long-term synaptic plasticity damage induced by repeated exposure of sevoflurane in neonatal rats

LIANG Xiao-li,GUI Huan,LIU Cheng-xi,ZHANG Chao,XU Shan,ZHANG Yi,ZHU Zhao-qiong   

  1. 1 Department of Anesthesiology, the Affiliated Hospital of Zunyi Medical University, Guizhou 563000, China; 2 Guizhou Key Laboratory of Anesthesia and Organ Protection; 3 Department of Anesthesiology, Zunyi Medical University
  • Received:2018-12-26 Revised:2019-01-21 Published:2019-03-15 Online:2019-04-24

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摘要： 目的 观察右美托咪定（Dex）预处理对新生期大鼠重复七氟醚吸入导致的远期突触可塑性损害的改善作用。方法 48只大鼠随机分为单纯七氟烷组（S组），Dex预处理组（DS组）以及空白对照组（C组），每组16只。S组于出生后7、14、21 d分别在腹腔注射3 mL/kg生理盐水后吸入七氟醚4 h，DS组将20 μg/kg右美托咪定溶于3 mL/kg生理盐水，于相同时间点腹腔注射后吸入七氟醚4 h，C组腹腔给予3 mL/kg生理盐水后放入相同环境中吸入运载气体4h。于37 d和97 d时分别从各组中随机选取8只大鼠行Morris水迷宫测试大鼠学习记忆能力，其后行在体电生理实 验比较各组海马CA1区神经元长时程增强和双脉冲易化（PPF）率。结果 在幼年期和成年期，与C组和DS组相比，S组逃避潜伏期明显延长，同时跨台次数减少（P＜0.05）。幼年期和成年期S组场兴奋性突触后电位（fEPSP）斜率在高频刺激后所有时间点的增幅均明显低于C组和DS组（P＜0.05），而PPF率在多个刺激间期高于C组与DS组（P＜0.05）。S组成年期在第1、2天的逃避潜伏期、在刺激间隔为50、100、150和200 ms时的PPF率明显低于幼年期，而跨台次数、在高频刺激后fEPSP斜率增幅显著高于幼年期（P＜0.05）。结论 右美托咪定可改善新生期大鼠重复吸入七氟醚所导致的长时程、短时程突触可塑性以及学习记忆能力的异常改变，这一作用可为临床上七氟醚对发育期大脑产生的不良影响提供新的防治策略。

关键词: 右美托咪定, 神经元可塑性, 突触, 七氟醚, 学习记忆能力

Abstract: Abstract: Objective To investigate the effect of dexmedetomidine (Dex) preconditioning on the long-term synaptic plasticity damage induced by repeated exposure of sevoflurane in neonatal rats. Methods Forty-eight rats were randomly assigned into sevoflurane group (group S), sevoflurane preconditioning group (group DS) and control group (group C), with 16 rats in each group. Rats in group S were intraperitoneally injected with 3 mL/kg normal saline before inhaling sevoflurane for 4 h at d7, d14 and d21. Rats in group DS were injected intraperitoneally with 20 μg/kg Dex dissolved in 3 mL/kg normal saline before 4 h sevoflurane inhalation at the same time points. Rats in group C inhaled carrier gas for 4 h after injecting 3 mL/ kg normal saline. Eight rats were randomly selected from each group at d37 and d97 to detect learning and memory ability by Morris water maze. Thereafter, in vivo electrophysiological experiments were implemented to compare the longterm potentiation (LTP) and paired-pulse facilitation (PPF) ratio in hippocampal neurons between three groups. Results At both juvenile and adult rats, comparing with rats in group C and group DS, the escape latency was remarkably prolonged in rats of group S, and the number of crossing through the target quadrant was reduced (P＜0.05). The increments of field excitatory postsynaptic potential (fEPSP) slope at all time points after high frequency stimulation were remarkably lower in rats of group S than those of group C and group DS (P＜0.05), while PPF ratio was significantly higher at multiple stimulus intervals in group S than group C and group DS (P＜0.05). As compared to group S at juvenile age, the escape latency at adult age was shortened in the first and second day in group S, and the number of crossing was increased. Meanwhile in the group S at adult age, the increment of fEPSP after high frequency stimulation was higher, and the PPF ratios induced by paired stimulation with interstimulus interval of 50 ms,100 ms,150 ms and 200 ms were obviously lower than those of group S at juvenile age (P＜0.05). Conclusion Dexmedetomidine can ameliorate the abnormal changes on the long-term and shortterm synaptic plasticity, as well as learning and memory ability, which could provide a new strategy for prevention and treatment of adverse effects on the developing brain induced by sevoflurane in clinical practice.

Key words: dexmedetomidine, neuronal plasticity, synapses, sevoflurane, learning and memory ability