Kamishoyosan potentiates pentobarbital-induced sleep in socially isolated, ovariectomized mice
Kamishoyosan potentiates pentobarbital-induced sleep in socially isolated, ovariectomized mice
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DOI：
10.1016/j.jep.2021.114585
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发表时间：
2021-08-31
影响因子：
5.4
通讯作者：
Iwasaki, Katsunori
中科院分区：
文献类型：
--
作者：
Egashira, Nobuaki;Goto, Yu;Iwasaki, Katsunori
民族药理学相关性：睡眠障碍是绝经前后妇女最常见的症状之一。Kamishoyosan （KSS）是一种用于治疗日本更年期妇女睡眠障碍的汉布药。然而，其确切的作用机制尚不清楚。目的：本研究通过对去卵巢小鼠进行社会隔离应激诱导，建立了一种新的绝经期睡眠障碍动物模型。以戊巴比妥诱导的睡眠时间为指标，我们旨在探讨KSS的影响和苯二氮卓类受体的参与。材料与方法：8周龄雌性小鼠，切除卵巢或假手术（对照组），社会隔离或群体饲养9周。将实验动物分为四组，分别是群居假手术组、孤立假手术组、群居切除卵巢组和社会隔离切除卵巢组。戊巴比妥（50mg /kg）腹腔注射（i.p）。睡眠时间被认为是翻正反射消失和恢复之间的一段时间（最长180分钟）。口服KSS （p.o.）。测试前60分钟。地西泮和氟马西尼分别于试验前30分钟和45分钟给予。在给药后的第二天，对小鼠实施安乐死，并对其子宫进行称重。结果：社会隔离、切除卵巢的小鼠睡眠时间比其他所有组的小鼠都短。在卵巢完整的小鼠中，地西泮（1 mg/kg，口服）显著延长戊巴比妥诱导的睡眠时间，但KSS （30-1000 mg/kg，口服）没有显著延长。然而，KSS （100 mg/kg, p.o）显著延长戊巴比妥诱导的社会隔离去卵巢小鼠睡眠时间。氟马西尼（3 mg/kg, ig）可逆转KSS介导的睡眠时间延长。结论：KSS增强戊巴比妥诱导的社会隔离去卵巢小鼠睡眠，苯二氮卓受体可能参与其药理机制。这些发现表明KSS对治疗绝经期睡眠障碍是有益的。
Ethnopharmacological relevance: Sleep disorders are among the most common symptoms in both peri- and postmenopausal women. Kamishoyosan (KSS) is a Kampo medicine prescribed for the treatment of sleep disorders in menopausal women in Japan. However, its precise mechanism of action remains unclear. Aim of the study: In the present study, we developed a new animal model of menopausal sleep disorders by inducing social isolation stress in ovariectomized mice. Using pentobarbital-induced sleeping time as an index, we aimed to investigate the effects of KSS and involvement of the benzodiazepine receptors. Materials and methods: Eight-week-old, female ddY mice were ovariectomized or subjected to a sham operation (control) and housed in social isolation or groups for 9 weeks. The animals were divided into four groups, grouphoused sham-operated, isolated sham-operated, group-housed ovariectomized, and socially isolated ovariectomized. Pentobarbital (50 mg/kg) was administered intraperitoneally (i.p.). Sleeping time was considered the period between the loss of righting reflex and its return (up to 180 min). KSS was administered orally (p.o.) 60 min before the test. Diazepam and flumazenil were administered i.p. 30 and 45 min before the test, respectively. On the day after administration, the mice were euthanized, and their uteri were weighed. Results: Socially isolated, ovariectomized mice had shorter sleeping times than mice in all other groups. In mice with intact ovaries, diazepam (1 mg/kg, i.p.) considerably prolonged the pentobarbital-induced sleeping time, but KSS (30-1000 mg/kg, p.o.) did not. However, KSS (100 mg/kg, p.o.) significantly prolonged the pentobarbital-induced sleeping time in socially isolated ovariectomized mice. The prolongation of sleeping time mediated by KSS was reversed by flumazenil (3 mg/kg, i.p.). Conclusions: KSS potentiated pentobarbital-induced sleep in socially isolated, ovariectomized mice, and the benzodiazepine receptors are possibly involved in its pharmacological mechanism. These findings suggest that KSS is beneficial for the treatment of menopausal sleep disorders.