文章摘要
右美托咪定对丙泊酚诱导新生大鼠大脑发育的远期影响
Long-term effects of dexmedetomidine on the brain development in propofol-induced neonatal rats
  
DOI：10.12089/jca.2018.02.015
中文关键词: 新生大鼠  右美托咪定  丙泊酚  海马  凋亡  认知功能
英文关键词: Neonatal rats  Dexmedetomidine  Propofol  Hippocampus  Apoptosis  Cognitive function
基金项目:国家自然科学基金(81373498,81060277);广西科学研究与技术开发计划项目(桂科攻1355005-4-2)
作者单位E-mail
陈佳林 530021,南宁市,广西医科大学第一附属医院麻醉科  
周丽芳 530021,南宁市,广西医科大学第一附属医院麻醉科  
韦祎 530021,南宁市,广西医科大学第一附属医院麻醉科  
陈静 530021,南宁市,广西医科大学第一附属医院麻醉科  
谢玉波 530021,南宁市,广西医科大学第一附属医院麻醉科 1157817791@qq.com 
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中文摘要:
      目的 探讨右美托咪定对丙泊酚诱导新生大鼠大脑发育的远期影响。方法 SD大鼠35只, 雌雄不拘, 7日龄,体重10～15 g, 采用随机数字表法随机分为七组: 生理盐水组(N组)、脂肪乳剂组(F组)、丙泊酚100 mg/kg组(P组)、右美托咪定75 μg/kg组(D组)、右美托咪定25 μg/kg+丙泊酚100 mg/kg组(PD25组)、右美托咪定50 μg/kg+丙泊酚100 mg/kg组(PD50组)、右美托咪定75 μg/kg+丙泊酚100 mg/kg组(PD75组), 每组5只。各组新生大鼠按相应给药方案处理。待大鼠苏醒后放回笼中继续饲养至9周时, 采用Morris水迷宫实验测定大鼠空间学习记忆能力;水迷宫实验结束后, 断头取脑, 制作脑组织切片, 采用TUNEL法检测海马神经细胞凋亡情况, 免疫组织化学法检测海马突触后致密蛋白95(PSD95)含量。结果 与N组比较, P组、PD25组和PD50组逃避潜伏期明显延长, 穿越原平台位置次数明显减少, 海马神经细胞凋亡率明显升高, 海马PSD95含量明显降低(P＜0.05)。与P组比较, PD50组、PD75组逃避潜伏期明显缩短, 穿越原平台位置次数明显增加, 海马神经细胞凋亡率明显降低(P＜0.05)；PD75组海马PSD95含量明显升高(P＜0.05)。与PD25组比较, PD50组和PD75组逃避潜伏期明显缩短, 穿越原平台位置次数明显增加, 海马神经细胞凋亡率明显降低(P＜0.05)；PD75组海马PSD95含量明显升高(P＜0.05)。与PD50组比较, PD75组海马神经细胞凋亡率明显降低, 海马PSD95含量明显升高(P＜0.05)。结论 应用右美托咪定50、75 μg/kg预处理可以减轻丙泊酚诱导致新生大鼠成年后认知功能障碍, 部分机制可能是通过减轻海马神经细胞凋亡和上调PSD95基因的表达;未见右美托咪定对发育期大脑有神经毒性。
英文摘要:
      Objective To explore the long-term effects of dexmedetomidine on the brain development in propofol-induced neonatal rats. Methods Thirty-five seven-day-old Sprague-Dawley rats of both genders, weighing 10-15 g, were randomly divided into seven groups (n=5) using a random number table: normal saline group (group N), intralipid group (group F), propofol 100 mg/kg group (group P), dexmedetomidine 75 μg/kg (group D), dexmedetomidine 25 μg/kg, 50 μg/kg and 75 μg/kg+propofol 100 mg/kg groups (groups PD25, PD50 and PD75), neonatal rats in each group were treated according to the corresponding dosing regimen. After fully awake, the rats were allowed to mature until postnatal week 9 and the spatial learning and memory capacities were tested by Morris water maze. The rats were sacrificed after the tests. Brain was sliced for determination of hippocampal apoptosis by TUNEL assays and the expression of postsynaptic density protein 95 (PSD95) by immunohistochemistry. Results Compared with group N, the escape latency was significantly prolonged, the times of platform crossing were significantly decreased, the hippocampal apoptosis ratio was significantly increased and the expression of PSD95 was significantly down-regulated in groups P, PD25 and PD50 (P＜0.05). Compared with group P, the escape latency was significantly shortened, the times of platform crossing were significantly increased and the hippocampal apoptosis were significantly decreased in groups PD50 and PD75 (P＜0.05), the expression of PSD95 was up-regulated in group PD75 (P＜0.05). Compared with group PD25, the escape latency was significantly shortened, the number of platform crossing was significantly increased and the hippocampal apoptosis were significantly decreased in groups PD50 and PD75 (P＜0.05), the expression of PSD95 was significantly up-regulated in group PD75 (P＜0.05). Compared with group PD50, the hippocampal apoptosis were significantly decreased, the expression of PSD95 was significantly up-regulated in group PD75 (P＜0.05). Conclusion The addition of dexmedetomidine 50, 75 μg/kg attenuates propofol-induced neurocognitive impairment in neonatal rats after aducthood, partially by attenuating hippocampal apoptosis and up-regulating the expression of PSD95. Dexmedetomidine alone was not neurotoxic to the developing brain.
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