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题名	慢性泼尼松龙注射诱导猕猴抑郁样表现及其机制探索
作者	李智飞
学位类别	硕士
答辩日期	2015-04
授予单位	中国科学院研究生院
授予地点	北京
导师	胡新天
关键词	猕猴 抑郁 可的松 HPA轴
其他题名	Chronic Prednisolone Injection Induced Depressive-like Behaviors and Investigation of the Mechanism
中文摘要	大量的研究结果表明抑郁症状的出现经常会伴随下丘脑-垂体-肾上腺轴（Hypothalamus-Pituitary- Adrenal Gland axis, HPA轴）的功能障碍：忧郁型抑郁病人可的松水平升高，创伤后抑郁（post-traumatic stress disorder, PTSD ）病人可的松水平降低。在动物模型中，经过肾上腺皮质酮慢性给药的大鼠和小鼠会表现出抑郁样的行为和生理症状。但是这些工作大部分都是建立在啮齿动物上的，而啮齿动物和人类在生理和行为等方面存在巨大的差异。为了弥补这个空白，我们选择用猕猴最为实验对象，通过肌肉注射可的松来直接控制其体内的可的松水平，从而验证可的松水平和抑郁发病之间的因果关系，并且建立抑郁的动物模型。 7只雄性猕猴分为两组，3只肌注可的松（15.9mg/kg），4只肌注相应体积的生理盐水， 共给药43天。测量指标为给药前后体重，糖水偏好，抑郁样行为，脑脊液单胺类递质水平，以及毛发和血液的可的松水平。 可的松组猕猴的体重没有变化，糖水消耗降低，这与其脑脊液中多巴胺水平的降低的结果是一致的。和生理盐水组的猕猴相比蜷缩行为的频率和持续时间都显著上升，自主活动、环境探索行为、刻板行为、自理毛行为的频率和持续时间也发生了显著的下降。 以上结果提示慢性泼尼松龙注射，可以扰乱HPA轴的稳态，最终导致抑郁症状的出现。
英文摘要	It has been observed that the occurrence of depressive symptoms is often accompanied by the dysfunction of HPA axis: patients with melancholic have elevated cortisol level and those with PTSD have depressed cortisol level. In animal models, rats and mice treated with high dose of corticosterone display many depressive-like behavioral and physical symptoms. But most of those works are based on ether human observations or rodent studies. To bridge this gap, we used rhesus macaques to establish the animal model of depression via manipulating their cortisol level. Seven male macaques were subjected to 43 days of either prednisolone acetate (3 monkeys) or saline (4 monkeys) injections (15.9mg/kg per day), and bodyweight, sucrose self-consumption, depressive-like behaviors, cerebrospinal fluid chemicals, and cortisol level in hair and plasma were measured. Bodyweights of the cortisol group decreased slightly, although the differences were not significant. Monkeys in the cortisol group consumed less sucrose solution than the saline group, indicating some sort of anhedonia. It is consistent with the finding that the cortisol group had lower CSF dopamine (DA) level. The frequency and duration of huddling-up both increased significantly in monkeys compared to saline group, while the frequency and duration of passive locomotion, environment exploration, stereotyped behaviors and self-grooming exhibited a considerable decreased. Our results indicated that chronic abnormally high dose prednisolone injection could disturb the homeostasis of HPA axis and eventually result in depressive symptoms.
语种	中文
内容类型	学位论文
源URL	[http://159.226.149.26:8080/handle/152453/10130]
专题	昆明动物研究所_神经系统编码
推荐引用方式 GB/T 7714	李智飞. 慢性泼尼松龙注射诱导猕猴抑郁样表现及其机制探索[D]. 北京. 中国科学院研究生院. 2015.

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