异丙酚诱导新生小鼠海马 NR2B 膜易位下调及空间记忆缺陷。
Propofol-induced downregulation of NR2B membrane translocation in hippocampus and spatial memory deficits of neonatal mice.
机构信息
Department of Anesthesiology Beijing Shijitan Hospital Capital Medical University Beijing China.
Department of Neurobiology and Center of Stroke Beijing Institute for Brain Disorders Capital Medical University Beijing China.
出版信息
Brain Behav. 2017 Jun 2;7(7):e00734. doi: 10.1002/brb3.734. eCollection 2017 Jul.
BACKGROUND
Thousands of infants and children are undergoing anesthesia around the world every day. But impacts of anesthetics on the developing neural system remain unclear yet. Previous evidence showed that anesthesia might affect the developing neural system. Thus, early-life anesthesia becomes a critical issue in clinical pediatric practice. Hence, propofol, a short-acting and widely applied intravenous anesthetic, has been gaining focus upon neonatal anesthesia.
METHODS
Fifty-four male C57BL/6J mice were randomly divided into following three groups: group D6 intraperitoneally (i.p.) injected propofol (100 mg/kg body weight) once a day from postnatal day 6 (P6) to P11, group D1 administrated propofol (100 mg/kg, i.p.) at P6 solely and administrated normal saline (10 ml/kg, i.p.) from P7 to P11, and group treated with normal saline (10 ml/kg, i.p.) from P6 to P11 as the control ( = 18 per group). Then, at P28, nine mice were collected randomly from each group for NR2B membrane translocation and phosphorylation analysis, and the rest half in each group were assigned to perform Morris water maze tests from P28 to P35.
RESULTS
Results showed that total protein expression levels of NR2B increased ( < .001) while its membrane translocation decreased ( < .001, = 9 per group) in the hippocampus but not in the prefrontal cortex of neonatal mice after repeated propofol administration. Phosphorylation levels of NR2B at serine 1303 (D1: < .05; D6: < .001, = 9 per group) and serine 1480 (D1: < .01, D6: < .001, = 9 per group) increased significantly as well in the hippocampus compared with group . In addition, memory deficits ( < .05, = 9 per group) were observed in Morris water maze tests of group D6 mice.
CONCLUSIONS
These results suggested that propofol exposure downregulates NR2B membrane translocation and causes spatial memory deficits, with a mediated increased NR2B protein expression and phosphorylation at Ser1303/1480 residues in the hippocampus of neonatal mice.
背景
全世界每天都有成千上万的婴儿和儿童接受麻醉。但是，麻醉对发育中神经系统的影响尚不清楚。先前的证据表明，麻醉可能会影响发育中的神经系统。因此，婴幼儿麻醉成为临床儿科实践中的一个关键问题。因此，丙泊酚作为一种短效且广泛应用的静脉麻醉剂，在新生儿麻醉中受到了关注。
方法
将 54 只雄性 C57BL/6J 小鼠随机分为以下三组：D6 组腹腔内（i.p.）注射丙泊酚（100mg/kg 体重），每天一次，从出生后第 6 天（P6）到 P11 天；D1 组仅在 P6 天注射丙泊酚（100mg/kg，i.p.），从 P7 天到 P11 天注射生理盐水（10ml/kg，i.p.）；D6 组注射生理盐水（10ml/kg，i.p.）作为对照，从 P6 天到 P11 天（每组=18 只）。然后，在 P28 天，从每组中随机抽取 9 只小鼠进行 NR2B 膜易位和磷酸化分析，其余一半小鼠从 P28 天到 P35 天进行 Morris 水迷宫测试。
结果
结果表明，在反复丙泊酚给药后，新生小鼠海马体中 NR2B 的总蛋白表达水平增加（<0.001），而其膜易位减少（<0.001，每组=9 只），但在大脑前额叶皮质中没有变化。NR2B 丝氨酸 1303 位点（D1：<0.05；D6：<0.001，每组=9 只）和丝氨酸 1480 位点（D1：<0.01，D6：<0.001，每组=9 只）的磷酸化水平也显著升高。此外，在 D6 组小鼠的 Morris 水迷宫测试中观察到记忆缺陷（<0.05，每组=9 只）。
结论
这些结果表明，丙泊酚暴露会下调 NR2B 膜易位，并导致空间记忆缺陷，同时伴有海马体中 NR2B 蛋白表达和丝氨酸 1303/1480 位点磷酸化的增加。
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