酸枣仁甲醇提取物促进日间快动眼睡眠的机制研究

Methanol Extract of Zizyphi Spinosi Semen Increases the REM Sleep of Daytime Associated Modulation Mechanism

目的探讨酸枣仁甲醇提取物(Methanol extract of Zizyphi Spinosi Semen,MEZSS)产生镇静效应与脑内γ-氨基丁酸(GABA)系统相关。方法经灌胃途径给予100mg/kg MEZSS后,检测大鼠的脑电图。经不同剂量MEZSS(2、4和8μg/mL)处理后,使用N,N二甲基二吖啶硝酸盐(MQAE)荧光探针检测小脑颗粒细胞内的氯离子浓度。在体内和体外,通过Western blot方法检测谷氨酸脱羧酶(GAD)和GABAA受体亚基的表达。结果 MEZSS能明显减少日间觉醒时间,延长REMS时间,尤其增加θ频率的睡眠。MEZSS以剂量依赖型的方式激活小脑颗粒细胞的氯离子通道。经MEZSS处理后,小脑颗粒细胞和大鼠下丘脑都能增加GAD和GABAA受体γ亚基的水平。结论在体内和体外MEZSS抑制神经元兴奋与激活GABA系统有关。

OBJECTIVE To investigate whether methanol extract of Zizyphi Spinosi Semen （MEZSS） has hypnotic effects through the γ-aminobutyric acid （GABA） ergic systems. METHODS The hypnotic effects of MEZSS were measured with elec- troencephalogram （EEG） activity in rats. Additionally, the chloride influx was estimated in primary cultured cerebellar granule cells with treatments of MEZSS or pentobarbital. On 1st day of treatments of MEZSS and diazepam, the GABAA receptor subunits and glutamic acid decarboxylase （GAD） expression was determined in hypothalamus in rat and cerebellar granule ceils. RESULTS During daytime, MEZSS increased the rapid eyemove （REM） sleep and the EEG θ-wave activity. In addition, both of MEZSS and pentobarbital increased chloride influx. MEZSS significantly increased GABAA receptors γ-subunit expres- sion and had no effect on the expression of α- and β- subunits. In addition, MEZSS enhanced expression of GAD, but pentobar- bital did not. CONCLUSION SMEZSS increases the REM sleep behaviors through the modification of GABAergic systems.