地塞米松对氯胺酮麻醉后幼鼠认知功能及海马Caveolin-1表达的影响

Effects of Dexamethasone on Cognitive Function and Caveolin-1 Expression in Hippocampus of Young Rats after Ketamine Anesthesia

目的:探讨地塞米松对氯胺酮麻醉致幼鼠认知功能的影响及机制。方法:选取30只SD幼鼠,随机分为正常对照组、氯胺酮组、氯胺酮+地塞米松组,每组10只。除正常对照组外,其余两组采用腹腔注射氯胺酮(50 mg·kg^-1)麻醉并行剖腹探查术,术前和术后氯胺酮+地塞米松组腹腔注射给药地塞米松(2.0 mg·kg^-1),1次/d,连续3 d,正常对照组和氯胺酮组腹腔注射等体积生理盐水。各组幼鼠进行Morris水迷宫实验,HE染色观察大鼠脑组织病理变化,Western blotting实验、免疫组化实验、Realtime PCR实验检测脑部海马组织中小窝蛋白-1(Caveolin-1)蛋白及基因表达水平。结果:定位巡航阶段第1天,氯胺酮组、氯胺酮+地塞米松组幼鼠逃避潜伏期均显著高于正常对照组(P<0.05),氯胺酮组与氯胺酮+地塞米松组幼鼠逃避潜伏期差异无统计学意义(P>0.05);从第2天开始,氯胺酮组幼鼠逃避潜伏期显著高于氯胺酮+地塞米松组与正常对照组(P<0.05)。与氯胺酮组比较,氯胺酮+地塞米松组幼鼠首次穿过平台所在象限需要的时间显著缩短,穿台次数显著增多(P<0.05);幼鼠海马组织Caveolin-1蛋白和mRNA表达水平显著升高(P<0.05)。病理组织学检查结果显示,氯胺酮+地塞米松组幼鼠大脑组织海马区神经元细胞形态明显改善。结论:地塞米松提高幼鼠脑组织Caveolin-1的表达改善氯胺酮麻醉手术后对学习记忆影响。

Objective:To investigate the effects of dexamethasone on cognitive function of young rats induced by ketamine anesthesia and underlying mechanism.Methods:Totally 30 young SD rats were randomly divided into the normal control group,ketamine group and ketamine+dexamethasone group with 10 rats in each group.In addition to the normal control group,the other two groups were treated with intraperitoneal injection of ketamine(50 mg·kg^-1)for laparotomy.Before and after the operation,ketamine+dexamethasone group was injected intraperitoneally with dexamethasone(2.0 mg·kg^-1),once a day for 3 consecutive days.The normal control group and ketamine group were injected intraperitoneally with saline with the same volume.Morris water maze test was performed on the 2nd day after the operation in each group.At the end of the recall experiment,rat brain tissues were withdrawn for HE staining to observe pathological changes.Western blot,immunohistochemistry and real-time PCR were used to detect Caveolin-1 protein and gene expressions in hippocampus.Results:On the 1st day of positioning cruise experiment,the escape latency of young rats in ketamine group and ketamine+dexamethasone group was significantly higher than that of the normal control group(P<0.05).There was no significant difference in the escape latency between ketamine group and ketamine+dexamethasone group(P>0.05).From the 2nd day,the escape latency in ketamine group was significantly higher than that in ketamine+dexamethasone group and the normal control group(P<0.05).Compared with that of ketamine group,the time required for ketamine dexamethasone group to pass through the quadrant of the platform was significantly shortened,and the number of passages was significantly increased(P<0.05),and the expressions of Caveolin-1 protein and mRNA in the hippocampus of young rats were significantly increased(P<0.05).The results of histopathological examination showed that the morphology of hippocampal neurons was significantly improved in ketamine+dexamethasone group.Conclusion:Dexamethasone can increase the expression of Caveolin-1 in brain tissue of young rats and improve the effect of ketamine anesthesia on learning and memory.