人参皂甙对大鼠自发睡眠结构的影响机制

 摘要：目的 研究人参皂甙（GS）调节自然睡眠的作用机制。方法 雄性SD大鼠随机分为对照、GS低(10 mg/kg)和高（100 mg/kg）剂量组。在大鼠体内植入无线发射器，术后按10和100mg/ kg GS或蒸馏水每日1次给大鼠灌胃，共6天。第1（急性）和6天（慢性）给药后，开始记录自由活动大鼠脑电活动12 h。在并列进行的另一个实验中，于大鼠给药第1和6天用乙醚麻醉后断头处死，取下丘脑组织检测GABAAergic系统蛋白表达情况。结果 GS 灌胃第1天，低剂量GS略微（P?>0.05）而高剂量显著增加非快动眼睡眠（NREM）和总睡眠而减少觉醒时间（P? <0.05）; 与对照组相比，GS低和高剂量均未改变大鼠下丘脑GAD蛋白表达（P? >0.05），但都增强了GABAA受体α、?亚型而没有影响?亚型表达（P? <0.05）。连续灌胃第6天，低、高剂量GS均显著增加NREM和总睡眠，减少觉醒（P? <0.05）；同时低剂量GS略微上调低剂量GS略微（P?>0.05）而高剂量GS显著增强大鼠下丘脑GAD蛋白表达水平（P? <0.05），但低、高剂量GS均未能影响GABAA受体表达（P? >0.05）。结论 GS能时间和剂量依赖性地调节大鼠的自然睡眠结构，其急性作用可能与下丘脑增加的GABAA受体α、?亚型蛋白表达有关，而慢性作用可能涉及经由上调GAD表达水平增加GABA产量。

Mechanism of Ginsenosides Regulating Spontaneous Sleep Architecture in Rats

Abstract: Objective To study the underling mechanism of the effect of ginsenosides(GS) on spontaneous sleep. Methods Adult SD rats were randomly divided into the control, GS 10 mg/kg (low dose) and 100 mg/kg (high dose) groups. Rats were instrumented with sleep-wake recording electrodes. After recovery from surgical operation, rats were orally administered GS 10 mg/kg and 100 mg/kg or water once per day for 6 days. On GS administration day 1 and day 6, Polygraphic signs of undisturbed sleep-wake activities were recorded for 12h (7:30 ~19:30) after GS administration. Results On GS administration day 1 (acute), 10 mg/kg GS slightly (P?>0.05 but 100mg/kg GS significantly (P?<0.05) increased the non-rapid eye movement (NREM) and total sleep and decreased wakefulness; compared with control, low dose and high dose GS failed to change the level of glutamic acid decarboxylase (GAD) (P?>0.05) but enhanced the expressions of GABAA receptor α,? not ? subunits in rat hypothalamus (P?<0.05). Following 6 days administration (chronic), both 10 and 100mg/kg GS increased markedly NREM and total sleep and decreased wakefulness. Accordingly, low dose GS slightly (P?>0.05) but high dose GS significantly (P? <0.05) increased the level of GAD in rat hypothalamus, whereas the expressions of GABAA receptor α, ? and ? subunits not affected (P?>0.05). Conclusion These results suggest that GS can regulate spontaneous sleep architecture in time and dose-dependent manner in which acute GS treatment is related to its up-regulating GABAA receptor α, ? subtypes whereas chronic GS administration involved in the raised GABA product produced by its over-expressing GAD in rat hypothalamus.