摘要目的 观察大鼠服用小儿麻醉前用药-咪达唑仑、氯胺酮口服液(Midazolum-ketamine oral solution,MKOS)后的不同时点大脑氮-甲基-D-天冬氨酸受体1(NMDAR1)和γ-氨基丁酸a受体(GABAAR)表达的变化,阐明MKOS的镇静作用机制.方法 选健康SD大鼠50只,随机分为10组,每组5只,分别在给药后0、5、10、15、30、60、90、120、240、360 min处死.0 min点为对照组,经灌胃器灌注2μl/g生理盐水,其他各组灌注2μl/g MKOS,每个时点5只.用40%多聚甲醛灌注固定,取大脑,制成冰冻及石蜡切片,采用免疫组织化学和原位杂交技术检测NMDAR1、GABAAR mRNA在大脑区的表达情况.所有数据应用显微荧光图像分析系统进行采集、分析,SPSS 11.5统计软件进行统计学处理.结果 (1)对照组大鼠脑神经胶质细胞NMDAR1表达多;服用MKOS 15 min后表达明显减弱,90 min后逐渐恢复,360 min基本恢复正常.(2)GABAAR mRNA也在神经胶质细胞中表达.对照组表达弱,给MKOS后30 min GABAAR表达增强,120 min后表达减少.结论 MKOS的镇静作用可能通过抑制兴奋性受体NMDAR1表达和增强GABAAR表达而实现.

abstractsObjective This study examined the effects of Midazolum-ketamine oral solution (MKOS) on the expression of N-methyl-D-aspartate receptor 1 (NMDAR1) and gamma-aminobutyric acid (GABA)A receptors (GABAAR) mRNA in the cerebral cortex of rat, in order to investigate the sedation mechanism of MKOS. Methods Fifty Sprague-Dawley(SD) rats were divided into ten groups according to the observed time after MKOS administration (0,5,10, 15,30,60,90,120,240 and 360 minutes, n =5 each). The 0 minute group(control group) received 0.9% saline instead. Immunohistochemical staining and in situ hybridization were used to detect the expressions of NMDAR1 and GABAAR mRNA in the cerebral cortex. Results Both GABAAR and NMDAR1 all expressed in the glial cells of cerebral cortex. The expression of NMDAR1 in control group was strong. The expression of NMDAR1 became weaker during 15 to 90 minutes after administration of MKOS (P＜0.05). The expression of GABAAR mRNA in control group was weaker,while became stronger during 30 to 90 minutes after administration of MKOS (P ＜0. 05). Conclusion MKOS may play sedation by strengthening the expression of GABAAR and suppressing the expression of NMDAR1 in the cerebral cortex.