异氟醚抑制老龄小鼠脑记忆提取及相关转录因子CREB的表达

目的:研究异氟醚对脑记忆提取及相关转录因子CREB合成的影响。方法 :老龄C57/BL6小鼠,接受Morris水迷宫定位航行训练,使其形成对隐蔽于水下平台定位的空间参考记忆后随机分为麻醉组、载气对照组和空白对照组,前两组分别接受异氟醚麻醉(4 h,1个最低肺泡有效浓度)、30%O24 h吸入,空白对照组不接受任何处理。于麻醉后1 d、1周和1个月重复位置回想测试,观察麻醉前、后平台象限距离百分比的变化。取已形成记忆的小鼠随机分为位置回想测试组、位置回想测试加麻醉组和空白对照组,分别接受位置回想测试、位置回想测试加异氟醚麻醉和无任何处理。于麻醉后1 d、1周和1个月重复位置回想测试。免疫荧光染色和实时定量RT-PCR分别检测位置回想测试后激活的脑CREB(p-CREB)表达和CREB mRNA水平。结果:麻醉前麻醉组平台象限距离百分与两个对照组相比无统计学差异,而麻醉后1 d和1周麻醉组平台象限距离百分比明显低于两个对照组,麻醉后1个月3组之间无统计学差异。麻醉后1 d,位置回想测试加麻醉组p-CREB的表达低于位置回想测试组(P<0.01)。结论:异氟醚麻醉可抑制老龄小鼠记忆提取及其相关的转录因子CREB的合成和激活。

Isoflurane impairs spatial memory recall and its related CREB expression in aged mice brain

Objective To investigate the effect of isoflurane on memory retrieval and on cAMP-response element binding protein(CREB) expression in aged mice brain.Methods Aged C57/BL6 mice were trained in Morris water maze(MWM) for 14 days.The criterion for memory formation is when the distal percentage of swimming in the quadrant of platform exceeds 30% in the probe test.After the acquisition of the memory in a hidden platform,the mice were allocated to isoflurane anesthetized group,oxygen control group and naive group.The mice of isoflurane anesthetized group were anaesthetized with isoflurane(1 minimal alveolar concentration,4 hours).The probe tests were repeated at 1 day,1 week and 1 month after anesthesia.The quadrant distance percentage of the three groups in different time points were compared.Mice with a formed memory were allocated to PRT group,PRT+Ane group and naive group which received only place recall test,place recall test plus anesthesia and no treatment respectively.The protein level of p-CREB in brain was detected by immunoflurescence and the mRNA level of CREB by real time RT-PCR.Results On 1 day and 1 week after anesthesia,the target quadrant distance percentage in anesthesia group was dramatically lower than that in the naive groups although no difference was found before anesthesia and 1 month after anesthesia.The mRNA expression of CREB after memory recall was significantly inhibited by isoflurane anesthesia on 1 day(P<0.01) and 1 week(P<0.01) after anesthesia.Although the level of p-CREB was inhibited on 1 day post-anesthesia(P<0.01),it recovered on 1 week after anesthesia.Conclusions Isoflurane anesthesia impairs memory retrieval and influences CREB expression and activation in aged mice.