丙泊酚诱导下调海马NR2B膜异位蛋白和小鼠空间记忆缺陷
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Propofol-induced downregulation of NR2B membrane translocation in hippocampus and spatial memory deficits of neonatal mice
背景和目的：每天都有成千上万的婴儿和儿童在世界各地接受麻醉。但麻醉药对神经系统发育的影响尚不清楚。过去的证据表明，麻醉可能会影响发育中的神经系统。因此，早期麻醉成为儿科临床实践中的关键问题。于是，丙泊酚作为一种短效且广泛应用的静脉麻醉药，已经成为新生儿麻醉的焦点。
方法：将54只雄性C57BL / 6J小鼠随机分成以下三组：D6组，从出生后第6天（P6）到出生后第11天（P11），每天一次腹腔注射（ip）丙泊酚（100mg / kg体重），在第六天单独给予D1组丙泊酚（ 100mg / kg，ip）和在第七天到第十一天施予生理盐水（10ml / kg，ip），在第六天和第十一天N组用生理盐水（10ml / kg，ip）处理作为对照（每组n = 18）。然后，在第二十八天，从每组中随机收集9只小鼠用于NR2B膜转位和磷酸化分析，并且将每组中的剩余一半分配用于进行从第28天至第35天的Morris水迷宫测试。与N组相比，丝氨酸1303（D1：p <.05; D6：p <.001，每组n = 9）和丝氨酸1480（D1：p <.01，D6：p <.001，n = 9 ）的NR2B磷酸化水平表达明显增加。此外，在D6组小鼠的Morris水迷宫试验中观察到其记忆缺陷（p <.05，每组n = 9）。
观点：结果表明，在反复使用丙泊酚给药后，NR2B的总蛋白表达水平在小鼠海马中增加（p <.001），而其膜转运减少（p <.001，每组n = 9），但在新生小鼠的前额叶皮质中却不存在。
讨论：这些结果表明丙泊酚暴露下调NR2B蛋白膜易位，并引起空间记忆缺陷，同时其介导NR2B蛋白表达增加和新生小鼠海马体中丝氨酸1303 / 1480残基的磷酸化。
1
方法：将54只雄性C57BL / 6J小鼠随机分成以下三组：D6组，从出生后第6天（P6）到出生后第11天（P11），每天一次腹腔注射（ip）丙泊酚（100mg / kg体重），在第六天单独给予D1组丙泊酚（ 100mg / kg，ip）和在第七天到第十一天施予生理盐水（10ml / kg，ip），在第六天和第十一天N组用生理盐水（10ml / kg，ip）处理作为对照（每组n = 18）。然后，在第二十八天，从每组中随机收集9只小鼠用于NR2B膜转位和磷酸化分析，并且将每组中的剩余一半分配用于进行从第28天至第35天的Morris水迷宫测试。与N组相比，丝氨酸1303（D1：p <.05; D6：p <.001，每组n = 9）和丝氨酸1480（D1：p <.01，D6：p <.001，n = 9 ）的NR2B磷酸化水平表达明显增加。此外，在D6组小鼠的Morris水迷宫试验中观察到其记忆缺陷（p <.05，每组n = 9）。
结果：结果表明，在反复使用丙泊酚给药后，NR2B的总蛋白表达水平在小鼠海马中增加（p <.001），而其膜转运减少（p <.001，每组n = 9），但在新生小鼠的前额叶皮质中却不存在。
讨论：这些结果表明丙泊酚暴露下调NR2B蛋白膜易位，并引起空间记忆缺陷，同时其介导NR2B蛋白表达增加和新生小鼠海马体中丝氨酸1303 / 1480残基的磷酸化。
Wang Y, Han S, Han R, et al. Propofol‐induced downregulation of NR2B membrane translocation in hippocampus and spatial memory deficits of neonatal mice[J]. Brain & Behavior, 2017, 7(7):e00734.
Abstract
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 N treated with normal saline (10 ml/kg, i.p.) from P6 to P11 as the control
(n = 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
(p < .001) while its membrane translocation decreased (p < .001, n = 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: p < .05;
D6: p < .001, n = 9 per group) and serine 1480 (D1: p < .01, D6: p < .001, n = 9 per group) increased significantly as well in the hippocampus compared with group N. In addition, memory deficits (p < .05, n = 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 mic
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