复方氯胺酮口服液对大鼠海马CA1 CA3区NMDA受体1 GABA_A受体mRNA表达的影响

Effects of compound ketamine oral solution on the expression of NMDA receptor 1 and GABAA receptor mRNA in CA1 and CA3 regions of hippocampus in rats

摘要:

目的：通过观察小儿麻醉前用药复方氯胺酮口服液(CKOS)对大鼠海马CA1、CA3区的γ氨基丁酸A受体(GABAAR)和氮甲基天冬氨酸受体1(NMDAR1)分布及其表达影响,探讨其镇静作用的机制。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0,5,10,15,30,60,90,120,240,360min处死。0min点为对照组,经灌胃器灌注2μL/g生理盐水,其它各组灌注2μL/gCKOS。采用免疫组化和原位杂交技术检测各组NMDAR1、GABAARmRNA在海马CA1、CA3区的表达和分布。结果：用药后海马CA1、CA3区的GABAARmRNA的表达逐渐增强,30～90min时受体表达最强,360min逐渐恢复用药前水平。NMDAR1在CA1、CA3区表达呈抑制状态。结论：CKOS能增强海马CA1、CA3区的GABAA受体的mRNA表达和抑制NMDAR1的表达,从而产生镇静作用,最终达到消除恐惧的目的。

Abstract:

OBJECTIVE: This study examined the effects of compound ketamine oral solution (CKOS ) on the expression of NMDAR_1 and GABA_AR mRNA in the CA1 and CA3 regions of the hippocampus in rats in order to investigate the mechanism of sedation for this medicine. METHODS: Fifty Spragus- Dawley rats were randomly assigned into ten groups according to the observed time after CKOS administration (0, 5, 10, 15, 30, 60, 90, 120, 240 and 360 minutes, n=5 each). The 0 minute group(Control group) received normal saline instead. Immune histochemistry staining and in situ hybridization were used to determine the expression and the distribution of NMDAR_1 and GABA_AR mRNA in the CA1 and CA3 regions of the hippocampus in various groups. RESULTS: The expressions of GABA_AR mRNA in the CA1 and CA3 regions of hippocampus were gradually increased after CKOS administration, with a significantly higher levels compared with those in the Control group at 30 and 90 minutes after administration. At 360 minutes the expression resumed to the similar levels to the Control group. The expressions of NMDAR_1 in the CA1 and CA3 regions of hippocampus were inhibited after CKOS administration, and were significantly lower compared with those in the Control group at each observed time point. CONCLUSIONS: CKOS may increase the GABA_AR mRNA expression and inhibit the NMDAR_1 expression in the CA1 and CA3 regions of the hippocampus in rats, which may be the underlying mechanism of sedation for this medicine.