自闭症大鼠模型中的右美托咪定和丙泊酚镇静需求
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Dexmedetomidine and propofol sedation requirements in an autistic rat model
背景与目的
自闭症是一种具有挑战性的神经发育障碍。过去的临床观察表明自闭症儿童的镇静需求有所改变。我们的研究旨在通过动物模型实验测试这种观察结果，并探索其可能的机制。
方 法
将8只成年怀孕的雌性SD大鼠随机分为两组。妊娠第12天给4例腹腔注射丙戊酸钠，4例注射等量生理盐水。在出生后第28天，对新生雄性大鼠进行进行旷场试验以确认自闭症特征。每只大鼠腹膜内注射丙泊酚 (50 mg/kg) 或右美托咪定 (0.2 mg/kg)。记录正常反射损失（LORR）和正常反射恢复（RORR）的时间。第二天，对所有大鼠进行再次镇静并记录其EEG。处死大鼠并评估海马GABAA受体、谷氨酸NMDA受体基因表达。
结 果
与对照相比，自闭症大鼠表现出更长的LORR时间以及更短的RORR时间（右美托咪定：12.0 versus 5.0 丙泊酚：22.0 and 8.0 for propofol; p < 0.05）。对照组大鼠在LORR两分钟后，脑电图显示低频率、高振幅波型。自闭老鼠表现出高频率、低振幅的清醒波形。在自闭大鼠中，海马GABAA受体基因表达明显减少，NMDA基因表达明显增加。
结 论
我们的研究支持了在对自闭症儿童麻醉时镇静药物需求增加的观察结论，并提出了一种机制。
原始文献摘要
Elmorsy S A, Soliman G F, Rashed L A, et al. Dexmedetomidine and propofol sedation requirements in an autistic rat model[J]. Korean Journal of Anesthesiology, 2018.
Background Autism is a challenging neurodevelopmental disorder. Previous clinical observations suggest altered sedation requirements for autistic children. Our study aimed to test this observation experimentally with an animal model and, to explore its possible mechanisms.
Methods Eight adult pregnant female Sprague Dawley rats were randomly selected into two groups. Four were injected with intraperitoneal sodium valproate on the gestational day 12 and four were injected with normal saline. On post-natal day 28 the newborn male rats were subjected to an open field test to confirm autistic features. Each rat was injected intraperitoneally with a single dose of propofol (50 mg/kg) or dexmedetomidine (0.2 mg/kg). Times to Loss of Righting Reflex (LORR) and to Return of Righting Reflex (RORR) were recorded. On the next day, all rats were re-sedated and their EEGs were recorded. The rats were sacrificed and hippocampal GABAA and glutamate NMDA receptor gene expression were assessed.
Results Autistic rats showed significantly longer time to LORR and a shorter time to RORR compared to controls (Median time to LORR: 12.0 versus 5.0 for dexmedetomidine and 22.0 and 8.0 for propofol; p < 0.05). EEG showed a low frequency, high amplitude wave pattern two minutes after LORR in control rats. Autistic rats showed a high frequency, low amplitude awake pattern. Hippocampal GABAA receptor gene expression was significantly less in autistic rats and NMDA gene expression was greater.
Conclusions This study in rat supports the clinical observations of increased anesthetic sedative requirements in autistic children and proposes a mechanism for it.
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