氯胺酮对未成年大鼠记忆维持及海马p-CREB、c-fos表达的影响

Effect of ketamine on memory consolidation,p-CREB and c-fos expression in hippocampal slices of infant rats

目的探讨氯胺酮(Ket)对未成年大鼠记忆维持能力及海马磷酸化环腺苷酸应答元件结合蛋白(p-CREB)、c-fos表达的影响及其相关性。方法筛选合格21日龄SD大鼠72只分为正常对照组、生理盐水组、假训练组、氯胺酮组(根据时间与剂量不同分为四个亚组:Ket1a、Ket1b:分别给与氯胺酮50mg/kg、100mg/kg腹腔注射后3d进行训练)。生理盐水组腹腔注射等体积的生理盐水。采用Y型迷宫进行学习记忆能力测试,应用免疫组化法检测海马p-CREB、c-fos的表达。结果与生理盐水组相比,Ket1a、Ket1b组大鼠记忆维持能力下降(P<0.05),同时海马神经元p-CREB、c-fos的表达减少(P<0.05);而Ket3a组、Ket3b组差异无统计学意义(P>0.05)。与正常对照组相比,其余各组海马神经元p-CREB、c-fos表达均增多(P<0.05)。而Ket1a和Ket1b或Ket3a和Ket3b组之间的行为学指标与免疫组化指标差异均无统计学意义(P>0.05)。结论氯胺酮可能通过抑制未成年大鼠海马p-CREB、c-fos的表达短期影响其记忆维持能力。

Objective To investigate the effect of ketamine （Ket） on memory consolidation, p-CREB and c-fos expression in the hippocampus of infant rats. Methods Seventy-two SD rats of 21 days old were divided into passive control group, normal saline group, pseudotraining group and Ket group, which were divided into four subsets according to the time and Ket dose. Ketla group and ketlb group were anesthetized with 50 mg/kg and 100 mg/kg Ket ip respectively, and were trained one day after Ket administration, Ket3a group and Ket3b group were anesthetized with 50 mg/kg and 100 mg/kg Ket ip respectively and were trained three days after Ket administration. Normal saline group rats were given equal volume of 0.9 % saline ip. Y-maze was used to test the ability of learning and memory on rats. p-CREB and c-fos protein were tested by immunhistochemistry. Results The memory consolidation in Ketla group and Ketlb group declined compared with that in normal saline group（P〈0.05）. The p-CREB and c-fos protein expressing cells in the hippocampus of Ketla group and Ketlbn group rats were fewer than those in normal saline group（P〈0. 05）. However, there was no significant difference between Ket3a group and Ket3b group. The number of p-CREB and c-los expressing cells was higher in normal saline group, pseudotraining group, Ketla group, Ketlb troup, Ket3a group and Ket3b group than that in passive control group. But the ability of memory consolidation and the number of p-CREB and c-fos expressing cells were not significantly different between Ketla group and Ketlb group or betweenn Ket3a group and Ket3b group. Conclusion Adminiistration of Ket may temporally affect the ability of memory consolidation of infant rats through suppressing expression of p-CREB and c-fos protein in the hippocampus.