慢性PCP猴睡眠障碍及奥氮平对其影响研究

发布时间：2018-02-24 01:25

本文关键词： 慢性PCP猴睡眠障碍奥氮平谷氨酸能　出处：《昆明医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：[背景和目的]临床中观察到精神分裂症患者合并睡眠障碍的发病率很高,其睡眠障碍的临床表现和病因众说纷纭,至今还没有一个统一的说法,其原因主要有:首先,精神分裂症相关病理生理机制和病因的研究结果很多来自于临床医生,因为受伦理限制而不能直接使用患者来做科研;其次,睡眠障碍缺乏客观的测量工具;而且很多实验属于观察性研究而非实验性研究。所以该实验目的主要是:1).在食蟹猴身上重复肌注苯环己哌啶(phencyclidine,PCP)诱导拟精神分裂症非人类灵长类动物模型(即慢性PCP猴),并研究该慢性PCP猴是否存在睡眠障碍;2).若慢性PCP猴存在睡眠障碍,那么奥氮平(Olanzapine,Ola)是否能逆转它;3).讨论慢性PCP猴作为精神分裂症合并睡眠障碍的动物模型的科学性;4).讨论小米运动手环作为研究睡眠障碍的可行性。[方法]在雌性食蟹猴身上反复肌注PCP诱导精神分裂症动物模型(即慢性PCP猴)后。实验一,分别将4只慢性PCP猴(实验组)与正常猴(对照组)放在在相同的环境中喂养,人为地建立昼夜节律后,用运动手环持续监测两组食蟹猴的睡眠情况,采集睡眠参数后,采用独立样本t检验对两组睡眠参数进行统计分析,看是否存在统计学意义。实验二,以实验一中慢性PCP猴的睡眠参数作为基线(baseline),然后给他们分别肌注小、大两种剂量的奥氮平(Ola1和Ola2),用小米运动手环分别持续监测baseline、Ola1和Ola2三组睡眠数据,采集相应的睡眠参数后,再把baseline与Ola1、baseline与Ola2分别进行配对比较,并把Ola2的睡眠参数与正常猴(对照组)的睡眠参数进行独立样本t检验。[结果]实验一.慢性PCP猴与正常对照组猴比较:相对与正常对照组,发现慢性PCP猴存在睡眠起始和睡眠持续性障碍,即睡眠潜伏期睡眠潜伏期(sleep onset latency,SOL)显著性延长,总清醒时间(total awake time, TAT)和睡后清醒时间(wake time after sleep onset,WASO)显著性增加,而总睡眠时间(total sleep time,TST)显著性减少及睡眠效率(sleep efficiency,SE)显著性降低;而睡眠结构方面,慢性PCP猴的深睡眠比值降低。实验二.baseline与Ola1、baseline与Ola2、Ola2与正常猴三组进行统计分析后发现:在睡眠起始及睡眠持续性方面,当予慢性PCP猴奥氮平治疗后,发现其SOL缩短,WASO减少,而TST和SE增加,且Ola2能完全逆转,从睡眠结构来看在给Ola1后无变化,而给Ola2后深睡眠比值增加。[结论]1.慢性PCP猴与精神分裂症患者的睡眠障碍表现相似,即SOL延长、WASO增加、TST减少和SE降低.2.奥氮平能改善慢性PCP猴的睡眠障碍,且大剂量奥氮平能完全逆转;3.通过重复肌注PCP诱导的精神分裂症模型(即慢性PCP猴)作为精神分裂症患者合并睡眠障碍的临床前的动物模型是有前景的,但需要进一步的多导睡眠仪(Polysomnography,PSG)验证。4.小米运动手环可以用于睡眠障碍的初筛和随访,但还不足以作为睡眠障碍的诊断工具。
[Abstract]:[background and objective] Clinical observation shows that the incidence of schizophrenia complicated with sleep disorders is very high, and the clinical manifestations and etiology of sleep disorders vary widely. So far, there has not been a unified explanation. The main reasons are as follows: first of all, Many studies on pathophysiological mechanism and etiology of schizophrenia come from clinicians, because they can not be directly used for scientific research because of ethical restrictions. Secondly, sleep disorders lack of objective measuring tools. And many of the experiments were observational rather than experimental. So the purpose of the experiment was mainly to: 1: 1.Induction of nonhuman primate models of schizophrenia (chronic) was induced by repeated intramuscular injection of phencyclidine PCPs in crab monkeys. PCP monkey, and study whether the chronic PCP monkey has sleep disorder. If the chronic PCP monkey has sleep disorder, So, can Olanzapine Olaa be able to reverse it? discuss the scientific nature of chronic PCP monkey as an animal model of schizophrenia with sleep disorder. Discuss the feasibility of millet exercise bracelet as a study of sleep disorder. [methods] in female diet. After repeated intramuscular injection of PCP to induce schizophrenic animal model (chronic PCP monkey) in crab monkey, experiment 1, Four chronic PCP monkeys (experimental group) and normal monkeys (control group) were fed in the same environment. After the circadian rhythm was established artificially, the sleep conditions of the two groups were continuously monitored with exercise bracelet, and the sleep parameters were collected. The independent sample t-test was used to analyze the sleep parameters of the two groups to see if there was statistical significance. In experiment two, the sleep parameters of chronic PCP monkeys were used as the baseline, and then they were given small intramuscular injection. Two different doses of olanzapine, Ola1 and Ola2, were used to continuously monitor the sleep data of baseline Ola1 and Ola2 with millet exercise bracelet. The corresponding sleep parameters were collected, and then baseline and Ola1 were paired with Ola2, respectively. The sleep parameters of Ola2 and normal monkey (control group) were tested by independent sample t test. [results] experiment 1. Comparison of chronic PCP monkey with normal control group: compared with normal control group, It was found that there were sleep initiation and sleep persistence disorders in chronic PCP monkeys, that is, sleep latency and sleep onset latencies were significantly prolonged, total awake time (tat) and wake time after sleep onsett (WASO) were significantly increased in chronic PCP monkeys. The total sleep time and sleep efficiency were significantly decreased, while the sleep structure, the sleep structure, the sleep efficiency and the sleep efficiency were significantly decreased, while the total sleep time and the sleep efficiency were significantly decreased, while the sleep structure, the sleep efficiency, the sleep efficiency and the sleep efficiency were significantly decreased. The ratio of deep sleep in chronic PCP monkeys was decreased. Experiment 2. The results of statistical analysis of baseline and Ola1 Olaeline and Ola2 Ola2 and normal monkeys showed that in sleep initiation and sleep persistence, SOL shortening and WASO were decreased after treatment with olanzapine in chronic PCP monkeys. However, TST and SE were increased, and Ola2 was reversed completely. The sleep structure did not change after Ola1, but the ratio of deep sleep increased after Ola2. [conclusion] 1. The sleep disorders of chronic PCP monkeys were similar to those of schizophrenic patients. That is, SOL prolongation of WASO increases the decrease of TST and SE. 2. Olanzapine can improve sleep disorder in chronic PCP monkeys. The model of schizophrenia induced by repeated intramuscular injection of PCP (chronic PCP monkey) as a preclinical animal model of schizophrenia with sleep disorder is promising. But it needs further polysomnography PSG verification .4.The millet sports bracelet can be used for the primary screening and follow-up of sleep disorders, but it is not enough to be used as a diagnostic tool for sleep disorders.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R740;R749.3

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