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糖皮质激素逆转七氟醚对大鼠记忆巩固的干扰效应
Glucocorticoid reverses the impairment of memory consolidation mediated by sevoflurane

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DOI:
作者:
薛景景，李强，曾庆文，薛庆生，曹晓华，张富军，于布为
Xue Jingjing, Li Qiang, Zeng Qingwen, Xue Qingsheng, Cao Xiaohua, Zhang Fujun, Yu Buwei
作者单位:
上海交通大学医学院附属瑞金医院麻醉科 华东师范大学脑功能基因组学教育部重点实验室和上海重点实验室
Department of Anesthesiolory, RuiJin Hospital, Shanghai JiaoTong University , School of Medicine, Shanghai 200025, China Shanghai Key Laboratory of Brain Functional Genomics, The Key Laboratory of Ministry of Education of China, East China Normal University, Shanghai 200062, China
关键词:
糖皮质激素；记忆巩固；七氟醚；α-氨基羟甲基恶唑丙酸受体
Glucocorticoid; Memory consolidation; Sevoflurane ; AMPA receptor
摘要:
目的 考察糖皮质激素对七氟醚介导的干扰记忆巩固效应的影响。方法 健康成年雄性Sprague-Dawley大鼠随机分为8组：对照组（Control组）、糖皮质激素（Glucocorticoid，GC）低中高剂量组（GC0.3、1.0、3.0mg/kg）；七氟醚组（Sevoflurane, Sevo组）、七氟醚+糖皮质激素低中高剂量组（Sevo +GC0.3、1.0、3.0mg/kg）。依据分组，在连续被动回避实验（continuous multiple-trial inhibition avoidance, CMIA）训练后即刻给予腹腔注射糖皮质激素（2ml/kg）或溶剂（2ml/kg），然后吸入30%氧气和70%氮气的空氧混合气（30% oxygen and 70% nitrogen）或2.0%七氟醚（Sevoflurane）2小时。24小时后行 CMIA记忆检测以及开场实验（Open field, OF）。根据行为学结果，选取Control组、GC3.0组、Sevo组及Sevo+GC3.0组每组5只大鼠，至吸入空氧混合气或七氟醚2小时结束后即刻处死，用于检测谷氨酸受体α-氨基羟甲基恶唑丙酸受体（α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor，AMPAR)亚基GluR1及GluR2在海马的表达水平。结果 与Control组比较，2.0%的七氟醚吸入2小时干扰了大鼠在CMIA任务中的记忆巩固（P＜0.05）。糖皮质激素能够以剂量依赖性的方式增强大鼠的记忆巩固，其中GC3.0组与Control组CMIA潜伏期的差异具有统计学意义（P＜0.05）。本研究中最大剂量的糖皮质激素（3.0 mg/kg）能够逆转七氟醚对大鼠CMIA记忆巩固的损害作用（P＜0.05）。糖皮质激素及七氟醚干预对学习后大鼠海马AMPAR亚基GluR1和GluR2的表达没有影响（P＞0.05）。结论 七氟醚损害记忆在海马的巩固，糖皮质激素能够逆转七氟醚对记忆巩固的干扰作用。
Objective To explore the effects of glucocorticoid on sevoflurane-induced impairment of memory consolidation and the mechanism. Methods Adult male Sprague-Dawley rats were randomized into eight groups: Control, GC0.3, GC1.0, GC3.0,Sevo, Sevo+GC0.3, Sevo+GC1.0, Sevo+GC3.0. Rats were received glucocorticoid (GC 0.3, 1.0, or 3.0 mg/kg, 2ml/kg, i.p.) or Vehicle (2ml/kg, i.p.) immediately after training in a continuous multiple-trial inhibition avoidance (CMIA) paradigm. Subsequently, the rats were exposed to sevoflurane (2.0% inspired) or air (30% oxygen and 70% nitrogen) for 2h. Twenty-four hours later, the CMIA retention latency and open field (OF) behavior were performed to test the influences of memory consolidation. According to results of the CMIA test, rats from the separate groups of Control、GC3.0、Sevo and Sevo+GC3.0 were killed immediately after inhalation for GluR1 and GluR2 subunits of AMPA receptor level quantification in the hippocampus. Results Compared to group Control, 2.0% Sevoflurane for 2h impaired memory consolidation on a 24-h test (P＜0.05). Glucocorticoid enhanced memory consolidation in a dose-dependent way. The memory retention latency of group GC3.0 was longer than that of group Control significantly (P＜0.05). Moreover, the largest dose of glucocorticoid (3.0 mg/kg) can block the sevoflurane-induced impairment of memory consolidation (P＜0.05). However there were no differences of GluR1 and GluR2 subunits of AMPA receptor expression among these four groups of Control、GC3.0、Sevo and Sevo+GC3.0. Conclusion The impaired effect of sevoflurane stems partly from its impairment of memory consolidation in the hippocampus, and glucocorticoid can block this effect.

 

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