跑步锻炼对抑郁症CUS模型大鼠海马各亚区内突触作用的体视学研究

发布时间：2019-04-21 17:31

【摘要】：目的:抑郁症是一种以心境低落为主要特征的精神情绪障碍性疾病。目前对该病的治疗主要包括抗抑郁药物治疗、电休克治疗,但以上治疗方式效果局限且患者承受的痛苦巨大;而跑步锻炼作为一种便捷有效、简单易行的治疗方式受到广泛关注。本实验拟利用慢性不可预知性应激(chronic unpredictable stress,CUS)模型大鼠对抑郁症海马各亚区内树突棘数量的改变情况以及跑步锻炼之后上述结构的改变情况进行研究。方法:雄性Sprague-Dawley(SD)大鼠,适应性喂养1周后根据糖水偏好试验进行筛查,剔除存在味觉障碍及糖水偏好不稳定的大鼠;利用旷场试验筛除有运动障碍的大鼠。将筛选出来的合格大鼠随机分为空白对照组和抑郁模型组:空白对照组大鼠共10只,5只/笼,正常喂养;抑郁模型组大鼠采用孤养模式,并给予为期4周的CUS应激,在建模第4周末采用糖水偏好试验和旷场试验结果筛选出成模大鼠共20只。将模型建立成功的抑郁模型组大鼠随机分为模型对照组和模型跑步组,每组各10只。给予模型跑步组的大鼠跑步训练,跑步方案为:水平跑台上的规律跑步锻炼,跑步速度设置为20 m/min,跑步时间设定为20 min/d、5 d/week,为期4周。每周固定时间测量各组大鼠体重。在跑步干预的第4周末对各组大鼠进行行为学测试,包括糖水偏好试验及旷场试验。行为学测试结束后,多聚甲醛灌注取脑,每组大鼠分别随机选取5只进行体视学定量研究。每只大鼠随机选取一侧大脑半球进行组织切片,制作成厚度为60μm的连续冰冻切片,按照1/6的抽样分数对所有含有海马的组织切片进行系统随机抽样(即每6张切片抽取1张,第一张在1~6之间随机选取),将每张切片进行免疫组织化学染色后在体视学显微镜下随机选取1~40个视野进行观察计数,并按照体视学方法对各组大鼠海马各亚区内树突棘密度及总数目进行计算。结果:1.4周CUS干预后,抑郁模型组大鼠的体重、糖水偏好百分比、旷场试验总评分均较空白对照组大鼠显著下降(p0.05);而跑步锻炼干预之后模型跑步组大鼠的体重、糖水偏好百分比、旷场试验总评分较模型对照组大鼠显著提高(p0.05)。2.与空白对照组相比,模型对照组大鼠海马CA1区、CA3区及DG内树突棘总数目显著下降(p0.05,p0.05,p0.05);而模型跑步组大鼠海马CA1区、CA3区及DG内树突棘总数目均较模型对照组显著增加(p0.01,p0.01,p0.01)。3.模型对照组大鼠海马CA1区、CA3区及DG内树突棘密度较空白对照组显著下降(p0.01,p0.01,p0.01);而与模型对照组相比,模型跑步组大鼠海马CA1区、CA3区及DG内树突棘密度增加,且差异均具有统计学意义(p0.01,p0.05,p0.05)。结论:1.本实验研究利用免疫组织化学方法及现代体视学手段对抑郁症模型大鼠海马CA1区、CA3区及DG内树突棘总数目及其密度进行研究,进一步证实了抑郁症海马内存在树突棘数目的丢失,说明树突棘的改变参与了抑郁症的发生发展。2.本实验的行为学结果与既往跑步锻炼可以改善抑郁症患者临床症状的研究一致,证明跑步锻炼的确对抑郁症模型大鼠具有治疗作用。3.利用跑步锻炼对抑郁症模型大鼠进行干预后发现,海马CA1区、CA3区及DG内树突棘总数目及密度显著增加,我们推测跑步锻炼调节海马内树突棘数目可能是跑步锻炼发挥其抗抑郁作用的重要结构基础之一。
[Abstract]:Objective: Depression is a mental and emotional disorder characterized by depression of state of mind. At present, the treatment of the disease mainly includes the treatment of anti-depression drugs and the treatment of electroshock, but the effect of the above treatment methods is limited and the suffering of the patients is great; and the running exercise is a convenient and effective and simple and feasible treatment mode. This experiment is to use the chronic unpredictable stress (CUS) model to study the changes of the number of dendritic spines in each subzone of the hippocampus and the change of the above-mentioned structure after running. Methods: Male Sprague-Dawley (SD) rats were screened according to the sugar water preference test after 1 week of adaptive feeding, and the rats with non-stable taste and sugar water preference were removed, and the rats with dyskinesia were screened by open-field test. The screened qualified rats were randomly divided into the blank control group and the depression model group:10 rats in the blank control group,5/ cage and normal feeding; the rats in the depression model group adopted the isolated mode, and the rats were given a 4-week CUS stress, In the fourth week of modeling,20 rats were selected from the model rats by the sugar-water preference test and the open-field test results. The model was randomly divided into two groups: model control group and model running group, each group of 10 rats. The running training of the rats in the model running group is given. The running scheme is as follows: the regular running exercise on the horizontal running table, the running speed is set to 20 m/ min, the running time is set to 20 min/ day, and the running speed is 5 days/ wek for 4 weeks. The weight of each group of rats was measured at a fixed time per week. Behavior tests were performed on each group of rats at the 4th weekend of running intervention, including the sugar water preference test and the open field test. After the end of the behavior test, the rats were filled with paraformaldehyde, and 5 rats were randomly selected for quantitative study. each rat randomly selects one side of the brain hemisphere for tissue slice, and is made into a continuous frozen section with a thickness of 60 & mu; m, and all the tissue sections containing the hippocampus are randomly sampled according to the sampling score of 1/6 (i. e.1 for every 6 slices), The first one was randomly selected between 1 and 6), and 1 to 40 visual fields were randomly selected for observation and counting under the stereological microscope, and the density and the total number of the dendritic spines in each subzone of the hippocampus of each group were calculated according to the stereological method. Results: After 1.4 weeks of CUS intervention, the weight and sugar water preference percentage of the model group in the depression model group were significantly lower than that of the blank control group (p0.05), and the weight and sugar water preference percentage in the model running group after the running exercise intervention. The total score of open field test was significantly higher than that of control group (p0.05). Compared with the blank control group, the total number of dendritic spines in the CA1 region, the CA3 region and the DG in the model control group decreased significantly (p0.05, p0.05, p0.05), while the total number of dendritic spines in the CA1 region, the CA3 region and the DG of the model running group was significantly increased compared with the control group (p0.01, p0.01, p0.01). In the model control group, the density of the dendritic spine in the CA1 region, the CA3 region and the DG group decreased significantly (p0.01, p0.01, p0.01) compared with the model control group, and the density of the dendritic spines in the CA1 region, the CA3 region and the DG of the model running group was increased compared with the model control group (p0.01, P0.05,p0.05). Conclusion:1. The total number and density of the dendritic spines in the hippocampal CA1 region, the CA3 region and the DG of the model rats of the depression model were studied by using the immunohistochemical method and the modern stereological method, and the loss of the number of dendritic spines in the hippocampus of the depression was further confirmed. The changes of dendritic spines have been involved in the development of depression. The results of behavior of this experiment and previous running exercise can improve the clinical symptoms of the patients with depression, and it is proved that the running exercise has a therapeutic effect on the depressed model rats. It was found that the total number and density of dendritic spines in the CA1 region, CA3 region and DG of the hippocampus were significantly increased with the intervention of the running exercise on the depression model rats, and it was suggested that the number of dendritic spines in the hippocampus CA1 region, the CA3 region and the DG could be one of the important structural bases of the running exercise to play an anti-depression effect.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R749.4

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