七氟醚-N2O麻醉对青年小鼠空间学习和记忆功能及pCREB和Egr1表达的影响

Effect of sevoflurane-N2O anesthesia on spatial learning and memory function and the expression of pCREB and Egr1 in young mice

目的研究七氟醚-N2O麻醉后青年小鼠的空间学习和记忆能力以及海马磷酸化环腺苷酸应答元件结合蛋白(phosphorylated cyclic AMP response element-binding protein,pCREB)和早期生长反应因子1(early growth response factor 1,Egr1)的表达,并与老年小鼠进行比较。方法12只3月龄和12只18月龄小鼠随机分为对照组和实验组,每组各6只。48 h后进行为期6天的获得训练。获得训练结束后24 h进行空间探索实验,实验结束后15 min收集两组小鼠的海马组织,通过Western blot和实时定量PCR方法评估pCREB和Egr1的表达水平。结果未见麻醉损害青年小鼠的空间学习和记忆功能以及海马中pCREB和Egr1的表达水平,麻醉组与对照组比较差异均无统计学意义;而老年小鼠Sev+N2O组在麻醉后第4、5、6天逃逸潜伏期显著长于对照组(P<0.05),两组小鼠游泳速度差异无统计学意义;在空间探索实验中,Sev+N2O组目标象限路程百分比和时间百分比显著低于对照组(P<0.01);海马中pCREB和Egr1的表达水平均较对照组显著下降(P<0.05)。结论七氟醚-N2O麻醉对青年小鼠的空间学习记忆能力没有损害,也不影响海马中pCREB和Egr1的表达,但会对老年小鼠造成损害。

Objective To investigate spatial learning and memory and expression of phosphorylated cyclic AMP response element-binding protein(pCREB)and early growth response factor 1(Egr1)in hippocampus of young mice anesthetized with Sevoflurane-nitrous oxide,compared with aged mice.Methods The mice aged 3 months(n=12)and 18 months(n=12)were randomly assigned to the experiment group and the control group,respectively,and there were 6 young mice and 6 old mice in each group.The mice in the experiment group were given 1.0 MAC sevoflurane,70%N2O and 30%oxygen for 4 h,while mice in the control group were given 30%oxygen for 4 h.A 6-day acquisition training was conducted 48 h after exposure.The probe trial was conducted 24 h after training.Collecting hippocampal tissues 15 min after the probe trial and the expression of pCREB and Egr1 were assessed by Western blot and real-time quantitative PCR.Results There was no significant difference in spatial learning and memory as well as the expression of pCREB and Egr1 in hippocampus between the Sev+N2O group and the control group in young mice.In aged mice,the escape latency of the Sev+N2O group was significantly longer compared with the control group on day 4,5 and 6(P<0.05).The difference of the swimming speed between the two groups was not significant.During the spatial probe test,the percentage of distance and time in the target quadrant of the Sev+N2O group was significantly lower than that of the control group(P<0.01).The expression of pCREB and Egr1 in the hippocampus was significantly decreased compared with the control group(P<0.05).Conclusion Sevoflurane-nitrous oxide anesthesia did not impair spatial learning and memory of young mice,nor did it affect the expression of pCREB and Egr1 in hippocampus,but it did impair the aged mice.