【摘要】：目的:抑郁癥是一種以心境低落為主要特征的精神情緒障礙性疾病。目前對(duì)該病的治療主要包括抗抑郁藥物治療、電休克治療,但以上治療方式效果局限且患者承受的痛苦巨大;而跑步鍛煉作為一種便捷有效、簡單易行的治療方式受到廣泛關(guān)注。本實(shí)驗(yàn)擬利用慢性不可預(yù)知性應(yīng)激(chronic unpredictable stress,CUS)模型大鼠對(duì)抑郁癥海馬各亞區(qū)內(nèi)樹突棘數(shù)量的改變情況以及跑步鍛煉之后上述結(jié)構(gòu)的改變情況進(jìn)行研究。方法:雄性Sprague-Dawley(SD)大鼠,適應(yīng)性喂養(yǎng)1周后根據(jù)糖水偏好試驗(yàn)進(jìn)行篩查,剔除存在味覺障礙及糖水偏好不穩(wěn)定的大鼠;利用曠場(chǎng)試驗(yàn)篩除有運(yùn)動(dòng)障礙的大鼠。將篩選出來的合格大鼠隨機(jī)分為空白對(duì)照組和抑郁模型組:空白對(duì)照組大鼠共10只,5只/籠,正常喂養(yǎng);抑郁模型組大鼠采用孤養(yǎng)模式,并給予為期4周的CUS應(yīng)激,在建模第4周末采用糖水偏好試驗(yàn)和曠場(chǎng)試驗(yàn)結(jié)果篩選出成模大鼠共20只。將模型建立成功的抑郁模型組大鼠隨機(jī)分為模型對(duì)照組和模型跑步組,每組各10只。給予模型跑步組的大鼠跑步訓(xùn)練,跑步方案為:水平跑臺(tái)上的規(guī)律跑步鍛煉,跑步速度設(shè)置為20 m/min,跑步時(shí)間設(shè)定為20 min/d、5 d/week,為期4周。每周固定時(shí)間測(cè)量各組大鼠體重。在跑步干預(yù)的第4周末對(duì)各組大鼠進(jìn)行行為學(xué)測(cè)試,包括糖水偏好試驗(yàn)及曠場(chǎng)試驗(yàn)。行為學(xué)測(cè)試結(jié)束后,多聚甲醛灌注取腦,每組大鼠分別隨機(jī)選取5只進(jìn)行體視學(xué)定量研究。每只大鼠隨機(jī)選取一側(cè)大腦半球進(jìn)行組織切片,制作成厚度為60μm的連續(xù)冰凍切片,按照1/6的抽樣分?jǐn)?shù)對(duì)所有含有海馬的組織切片進(jìn)行系統(tǒng)隨機(jī)抽樣(即每6張切片抽取1張,第一張?jiān)?~6之間隨機(jī)選取),將每張切片進(jìn)行免疫組織化學(xué)染色后在體視學(xué)顯微鏡下隨機(jī)選取1~40個(gè)視野進(jìn)行觀察計(jì)數(shù),并按照體視學(xué)方法對(duì)各組大鼠海馬各亞區(qū)內(nèi)樹突棘密度及總數(shù)目進(jìn)行計(jì)算。結(jié)果:1.4周CUS干預(yù)后,抑郁模型組大鼠的體重、糖水偏好百分比、曠場(chǎng)試驗(yàn)總評(píng)分均較空白對(duì)照組大鼠顯著下降(p0.05);而跑步鍛煉干預(yù)之后模型跑步組大鼠的體重、糖水偏好百分比、曠場(chǎng)試驗(yàn)總評(píng)分較模型對(duì)照組大鼠顯著提高(p0.05)。2.與空白對(duì)照組相比,模型對(duì)照組大鼠海馬CA1區(qū)、CA3區(qū)及DG內(nèi)樹突棘總數(shù)目顯著下降(p0.05,p0.05,p0.05);而模型跑步組大鼠海馬CA1區(qū)、CA3區(qū)及DG內(nèi)樹突棘總數(shù)目均較模型對(duì)照組顯著增加(p0.01,p0.01,p0.01)。3.模型對(duì)照組大鼠海馬CA1區(qū)、CA3區(qū)及DG內(nèi)樹突棘密度較空白對(duì)照組顯著下降(p0.01,p0.01,p0.01);而與模型對(duì)照組相比,模型跑步組大鼠海馬CA1區(qū)、CA3區(qū)及DG內(nèi)樹突棘密度增加,且差異均具有統(tǒng)計(jì)學(xué)意義(p0.01,p0.05,p0.05)。結(jié)論:1.本實(shí)驗(yàn)研究利用免疫組織化學(xué)方法及現(xiàn)代體視學(xué)手段對(duì)抑郁癥模型大鼠海馬CA1區(qū)、CA3區(qū)及DG內(nèi)樹突棘總數(shù)目及其密度進(jìn)行研究,進(jìn)一步證實(shí)了抑郁癥海馬內(nèi)存在樹突棘數(shù)目的丟失,說明樹突棘的改變參與了抑郁癥的發(fā)生發(fā)展。2.本實(shí)驗(yàn)的行為學(xué)結(jié)果與既往跑步鍛煉可以改善抑郁癥患者臨床癥狀的研究一致,證明跑步鍛煉的確對(duì)抑郁癥模型大鼠具有治療作用。3.利用跑步鍛煉對(duì)抑郁癥模型大鼠進(jìn)行干預(yù)后發(fā)現(xiàn),海馬CA1區(qū)、CA3區(qū)及DG內(nèi)樹突棘總數(shù)目及密度顯著增加,我們推測(cè)跑步鍛煉調(diào)節(jié)海馬內(nèi)樹突棘數(shù)目可能是跑步鍛煉發(fā)揮其抗抑郁作用的重要結(jié)構(gòu)基礎(chǔ)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.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R749.4

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