笼养食蟹猴自发抑郁模型的创建与验证

发布时间：2018-06-08 18:41

本文选题：抑郁症 + 非人灵长类　；参考：《重庆医科大学》2015年博士论文

【摘要】：背景：抑郁症,目前已经成为一种影响全球的精神疾病,成为仅次于癌症,危害公众的二号公敌。抗抑郁治疗收效甚微,复发率较高,这不仅加重了个人和家庭的负担,还对于整体社会发展而言,负面影响极强。关于抑郁疾病的发病机制,人类的认识还较为肤浅；尽管,我们所使用啮齿类动物抑郁模型,在很大程度上推动了人类对抗抑郁治疗的认识进程；然而该物种无论从进化程度,还是从高级情感活动与灵长类动物还存在较大差异,较难模拟人类疾病的特征。为此,我们选取高级非人灵长类动物作为研究对象,构建更类似人类重型抑郁症特征的灵长类抑郁模型。目的：创建与验证笼养食蟹猴自然发生抑郁模型；方法：实验一,通过对随机选取的10只成年雌性食蟹猴,并记录隔离前所在大笼的生活行为,再随机分为社会隔离组和社会隔离叠加视觉隔离组,社会隔离90天后,返回原来生活的大笼环境,对比隔离前后行为的变化,建立抑郁行为的参考标准；实验二,通过选取每笼内等级较低,行为表现迟滞的食蟹猴,作为自发抑郁模型的初选样本,进一步根据Shively报道的食蟹猴抑郁标准,再次遴选,并系统观察所有个体,对比其与社会隔离所致抑郁个体和正常个体之间的差异；实验三,验证抑郁所致生物个体代谢的异同,通过抽取自发抑郁个体和正常个体的血液,进行代谢组学分析,比较代谢差异。结果：社会隔离使食蟹猴社会交互行为、运动行为显著减少,而且表现出对后代和群体之间的友好行为冷漠,个体喜欢独坐蜷缩,且对食物或外来刺激毫无兴趣；白发抑郁个体与社会隔离致抑郁模型,具有相似的行为特点;而且其体内的氨基酸代谢变化,与健康对照组相比,自发抑郁组内高水平表达的有硅烷胺,苯甲酰胺,景天庚酮糖和甘油；相对于对照组低表达的有尿素,亮氨酸,丝氨酸,苏氨酸,丁酸,苏糖醇,甲硫氨酸,脯氨酸,苯丙氨酸,天冬酰胺,单胺酸,2-酮基葡糖酸,阿拉伯呋喃糖,磷酸,鸟氨酸,柠檬酸,1,4-丁二胺,果糖,葡萄糖,肌醇,松二糖,α-D-吡喃葡糖苷；更进一步的差异代谢产物功能性分析结果显示,自发抑郁组内,氨基酸的代谢紊乱,包括亮氨酸,丝氨酸,苏氨酸,甲硫氨酸,脯氨酸,苯丙氨酸,天冬酰胺,鸟氨酸；这与在啮齿类抑郁模型和临床抑郁患者的代差异物表现一致。结论：社会隔离模型提供了稳定的抑郁行为依据,群养食蟹猴自发抑郁模型,依据自然发展规律自发形成,尚未添加任何人为干预要素,有效的模拟抑郁发病机制的要素,有望成为可靠的抑郁机制的研究载体。
[Abstract]:Background: depression has become a global mental disorder, second only to cancer, the second enemy to the public. Antidepressant therapy has little effect and high recurrence rate, which not only increases the burden of individuals and families, but also has a strong negative effect on the overall social development. Human understanding of the pathogenesis of depressive diseases is relatively superficial; although the rodent model of depression we use has largely contributed to the cognitive process of antidepressant therapy, the species has evolved to a greater degree. It is difficult to simulate the characteristics of human diseases because of the difference between advanced affective activities and primates. Therefore, we select advanced non-human primates as the research object, and construct a primate depression model which is more similar to the characteristics of human severe depression. Objective: to establish and verify the depression model of cage feeding crab monkey. They were randomly divided into social isolation group and social isolation superimposed visual isolation group. After 90 days of social isolation, they returned to their original cage environment, compared the changes of behavior before and after isolation, and established reference criteria for depressive behavior. By selecting the crab monkey with lower grade in each cage and tardy behavior, as the primary sample of the spontaneous depression model, we further re-selected the crab monkey according to the depression criteria reported by Shively, and observed all the individuals systematically. The third experiment was to verify the similarities and differences of metabolism between the depressive individuals and the normal individuals, and to analyze the metabolism of the depressive individuals and normal individuals by extracting the blood of the individuals with spontaneous depression and normal individuals. Comparison of metabolic differences. Results: social isolation significantly reduced the social interaction behavior and movement behavior of crab eating monkeys, and showed indifference to the friendly behavior between offspring and groups. Individuals preferred to sit alone and curl up, and they were not interested in food or external stimuli. The depression model caused by social isolation had similar behavioral characteristics, and the changes of amino acid metabolism in the body were higher in the spontaneous depression group than those in the healthy control group, such as silanamine and benzoamide. Compared with the control group, there were low expression of urea, leucine, serine, threonine, butyric acid, threonol, methionine, proline, phenylalanine, asparagine, monoamine 2-ketoglucoic acid. Arabinose, phosphoric acid, ornithine, citric acid, 4-butylenediamine, fructose, glucose, inositol, loose disaccharide, 伪 -Dpyranoside; functional analysis of further differential metabolites showed that in the spontaneous depression group, The metabolic disorders of amino acids, including leucine, serine, threonine, methionine, proline, phenylalanine, asparagine, ornithine, were consistent with those in rodent depression models and in patients with clinical depression. Conclusion: the social isolation model provides a stable basis for depressive behavior. The spontaneous depression model of feeding crab-eating monkeys spontaneously forms according to the natural development law, and no human intervention elements have been added to effectively simulate the factors of depression pathogenesis. It is expected to be a reliable carrier for the study of the mechanism of depression.
【学位授予单位】：重庆医科大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R749.4;R-332

【相似文献】