糖皮质激素逆转七氟烷对大鼠记忆巩固的干扰效应  

Glucocorticoid reverses the impairment of memory consolidation mediated by sevoflurane

作　　者：薛景景[1] 李强[1] 曾庆文[2] 薛庆生[1] 曹晓华[2] 张富军[1] 于布为[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院麻醉科,上海200025 [2]华东师范大学教育部和上海市脑功能基因组学重点实验室

出　　处：《上海医学》2013年第2期126-130,共5页Shanghai Medical Journal

基　　金：国家自然科学基金(81072703、30901410);上海市科学技术委员会基金(10ZR1419700)资助项目

摘　　要：目的探讨糖皮质激素对七氟烷介导的干扰记忆巩固效应的影响。方法将健康成年雄性Sprague-Dawley大鼠随机分为对照组、糖皮质激素低剂量(GC0.3)组、糖皮质激素中剂量(GC1.0)组、糖皮质激素高剂量(GC3.0)组、七氟烷(Sevo)组、七氟烷+糖皮质激素低剂量(Sevo+GC0.3)组、七氟烷+糖皮质激素中剂量(Sevo+GC1.0)组、七氟烷+糖皮质激素高剂量(Sevo+GC3.0)组。在连续被动回避实验(CMIA)训练后即刻,GC3.0组、Sevo+GC3.0组均予腹腔注射糖皮质激素0.3mg/kg,GC1.0组、Sevo+GC1.0组均予腹腔注射糖皮质激素1.0mg/kg,GC3.0组、Sevo+GC3.0组均予腹腔注射糖皮质激素3.0mg/kg,上述注射剂量均为2mL/kg;对照组、Sevo组均予腹腔注射乙醇稀释液2mL/kg。随后再分别吸入含氧体积分数为0.3的空氧混合气体(体积分数为0.3的氧气和体积分数为0.7氮气)或体积分数为0.02的七氟烷2h。24h后,每组选取14只大鼠行CMIA记忆检测及开场(OF)实验。再根据行为学结果,选取对照组、GC3.0组、Sevo组及Sevo+GC3.0组各5只大鼠,置于空氧混合气体中或吸入体积分数为0.02的七氟烷2h后即刻处死,检测海马中谷氨酸受体α-氨基羟甲基恶唑丙酸受体亚基GluR1及GluR2的表达水平。结果 GC3.0组大鼠的CMIA记忆潜伏期显著长于对照组(P<0.05),Sevo组的CMIA记忆潜伏期显著短于对照组及Sevo+GC3.0组(P值均<0.05)。单因素方差分析显示,各组间在OF实验中600s的运动速度、运动距离和中央区时间的差异均无统计学意义(P值均>0.05)。双因素方差分析显示,GC3.0组、Sevo组及Sevo+GC3.0组大鼠经CMIA学习后2h大鼠海马GluR1、GluR2的表达水平与对照组的差异均无统计学意义(P值均>0.05)。结论七氟烷损害记忆在海马的巩固,糖皮质激素能够逆转七氟烷对记忆巩固的干扰作用。Objective To explore the effects of glucocorticoid on sevoflurane-induced impairment of memory consolidation. Methods Healthy adult male Sprague-Dawley rats were randomized into eight groups： control, GC0.3, GC 1.0, GC 3.0, Sevo, Sevo＋GC 0.3, Sevo＋GC 1.0 and Sevo＋GC 3.0 groups. Immediately after a continuous multiple-trial inhibition avoidance （CMIA） training, rats in GC 0.3 and Sevo＋ GC 0.3 groups, GC 1.0 and Sevo＋ GC 1.0 groups, GO 3.0 and Sevo ＋ GC 3.0 groups received peritoneal injection of glucocorticoid at 0.3 mg/kg （~2 mL/kg）, 1.0 mg/kg （ 2 mL/kg）, and 3.0 mg/kg（2 mL/kg）, respectively; rats in Control and Sevo groups received peritoneal injection of ethanol diluent （2 mL/kg）. Then the rats were exposed to sevoflurane （2.0% inspired） or air （30% oxygen and 70% nitrogen） for 2 hours. Twenty-four hours later, the CMIA retention latency and open field （OF） behavior were performed in 14 rats of each group. According to results of CMIA test, 5 rats from control, GO 3.0, Sevo and Sevo＋ GO 3.0 groups were sacrificed. The levels of GluR1 and GluR2 subunits of a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor （AMPAR） in the hippocampus were measured. Results The memory retention latency of GO3.0 group was significantly longer than that of control group （P〈0.05）. The memory retention latency of Sevo group was significantly shorter thanthose of control and Sevo＋ GO 3.0 group （both P〈O. 05）. One-factor analysis of variance showed that there were no significant differences in moving speed, moving distance or time in central region in the 600 seconds after open field between the rats with or without glucocorticoid （all P〉0.05）. Two-factor analysis of variance showed that there were no significant differences in the levels of GluR1 and GluR2 subunits among control, GO3.0, Sevo and Sevo＋ GC3.0 group （all P〉O. 05）. Conclusion Glucocorticoid can block the sevoflurane-induced impairment of memory consolidation in the hippocampus.

关 键 词：糖皮质激素 记忆巩固 七氟烷 α-氨基羟甲基恶唑丙酸受体 

分 类 号：R363[医药卫生—病理学]