氯胺酮对成年小鼠海马神经元p-ERK1／2表达和学习记忆能力的影响

The effect of ketamine on p- ERK1/2 expression in hippocampal neurons and the ability of learning behavior in adult mice

目的研究氯胺酮对成年小鼠海马神经元P—ERK1／2表达和学习记忆能力的影响。方法成年雄性昆明小鼠分为生理盐水组（16ml／kg）、氯胺酮K1组（50mg／kg）、氯胺酮K2组（100mg／kg）和氯胺酮K3组（200mg／kg）。氯胺酮K3组又分为K3a组（6h）、K3b组（12h）和K3c组（24h），每组各10只，每组连续腹腔注射不同剂量氯胺酮7天，每天1次。采用Y迷宫进行记忆能力测试；提取海马组织总蛋白，免疫印迹检测P—ERK1／2表达。结果与生理盐水组相比，K1组和K2组成年小鼠学习记忆保持率、P—ERK1／2表达的差异无统计学意义（P〉0．05），而K3组成年小鼠学习记忆保持率、P—ERK1／2表达均低于生理盐水组、K1组和K2组（P〈0．05）。结论过量氯胺酮可能通过抑制成年小鼠海马神经元P—ERK1／2表达损害其学习记忆能力。

Objective To investigate the effect of ketamine on p - ERK1/2 expression in hippocampal neurons and the ability of learning behavior in adult mice. Methods Adult male Kunming mice were divided into normal saline group （ 16 ml/kg）, ketamine group （ K1 ） （50 mg/kg）, ketamine group （K2） （ 100 mg/kg） and ketamine group （K3） （200 mg/kg）. K3 group was fresher subdivided into three groups （ n = 10 each） ： ketamine K3a group （6 h）, K3b group （ 12 h） and K3c group （24 h） , treated with daily intraperitoneal injection for 7 consecutive days. Y maze was used to test memory ability; total proteins in hippoeampus were extracted and the expression of p - ERK1/2 was tested by Western blotting. Results Compared with the saline group, the rate of learning and memory retention, p - ERK1/2 expressions in K1 and K2 groups had no statistical significance （ P 〉 0.05 ） , while the rate of learning and memory retention, p - ERK1/2 expressions statistically descended （ P 〈 0.05 ） in K3 group. Conclusion Overdose of ketamine could impair the learning and memory in adult mice, which might be mediated by the downregulation of p- ERK1/2 expression in the hippocampal neurons.