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学科主题药理学
反复给予皮质酮模拟慢性应激引起大鼠睡眠特征的研究
杨光
2016-05-19
学位类型硕士
导师张永鹤
专业药理学
授予单位北京大学
授予地点北京大学基础医学院
学位硕士
关键词皮质酮 睡眠障碍 抑郁样行为 糖皮质激素受体 盐皮质激素受体
其他题名The acteristics of sleep disorder induced by onic administration of corticosterone in rats.
分类号R963
页数69
摘要

长期应激所致的糖皮质激素持续升高可引起许多严重的生理和心理疾病,如抑郁、焦虑以及睡眠障碍。其中,睡眠障碍主要表现为睡眠质量下降、睡眠持续时间减少和睡眠结构异常等改变。本课题旨在对糖皮质激素模拟应激过程中伴发的睡眠障碍与抑郁行为二者之间的相关性进行初步研究,并试图对其潜在机制进行探索。

本研究采用大鼠睡眠时相分析、行为学检测、蛋白印迹及高效液相色谱等实验方法,研究长期给予皮质酮中(第7、14和21天)对睡眠以及行为的影响。研究了睡眠和情绪调节相关核团中的活性和递质变化,同时检测了相关核团糖皮质激素受体(GR)和盐皮质激素受体(MR)的改变。

结果发现通过连续给予皮质酮(40 mg/kg, s.c.)能够建立起稳定的伴有睡眠障碍的抑郁动物模型。经相关性分析,发现某些睡眠参数与抑郁行为之间存在相关性。此外,第7天时动物的睡眠障碍以觉醒增加为主,第14天和第21天时的睡眠障碍以快眼动睡眠脱抑制为主。初步机制研究发现,睡眠和抑郁相关的脑区,如蓝斑核(LC)、VLPO、LDT以及PPT等脑区的活性以及GR和MR水平均出现变化,且变化程度不一致。

由此得出结论:

糖皮质激素水平升高可模拟应激状态,引起显著的睡眠障碍和抑郁行为。

睡眠障碍可能对抑郁行为形成有促进作用,同时抑郁症状也会引起睡眠障碍。

GR和MR功能以及相关脑特异性的变化可能与脑内睡眠调控环路和情绪相关脑区的异常有关。

英文摘要

The sustained elevation of plasma glucocorticoid was implicated in serious physical and psychological diseases, such as depression, anxiety and sleep disorder. Among others, sleep disorder was acterized by compromised sleep quality and sleep continuity, as well as alteration of sleep architecture. This study aims to make a preliminary investigation on the potential relationship between sleep disturbance and depressive behaviors throughout the stress status mimicked by long-term glucocorticoid exposure, and to explore its underlying mechanism.

Effects of corticosterone administration for 7, 14 and 21 days on sleep pattern and animal behaviors were investigated by using sleep polygraphic recording and analysis, a battery of behavior tests, western blot analysis and HPLC assay. The activity of and neurotransmitters in sleep and emotion regulating brain nucleus were determined. The protein levels of glucocorticoid receptor and mineralocorticoid receptor in these areas were also measured.

A depression animal model with pre-existing sleep disorders was established by onic administration of corticosterone (CORT, 40 mg/kg, s.c.). The results of present study showed that the abnormal changes of some parameters are correlated with the development of depressive-like behaviors. After 7 days treatment of CORT the time spent in wakefulness ware prolonged day-by-day. After 14 and 21 days treatment, the REM sleep disorders became increasingly prominent. This study indicated that the acticity and GR/MR function of some brain areas involed in sleep and depression regulation, such as LC, VLPO and LDT/PPT were heterogeneously changed.

From the results we presumed that:

Chronic elevation of glucocorticoid level may induce a stress mimetic state and lead to sleep disturbances.

Sleep disorders may precipitate the emergence of depressive-like behaviors. On the other hand, the depressive-like behaviors may exacerbate the sleep disorsers.

The alterations of GR and MR as well as the specific brain area may be involed in the neural circuits which was responsible for the sleep and emotions disorders.

语种中文
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文献类型学位论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/149429
专题北京大学基础医学院
北京大学第三临床医学院_老年内科
作者单位北京大学基础医学院
第一作者单位北京大学基础医学院
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杨光. 反复给予皮质酮模拟慢性应激引起大鼠睡眠特征的研究[D]. 北京大学基础医学院. 北京大学,2016.
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