【摘要】：目的:建立條件恐懼應(yīng)激模型,對(duì)條件恐懼應(yīng)激條件下大鼠應(yīng)激反應(yīng)和腦損傷相關(guān)指標(biāo)進(jìn)行綜合的檢測(cè)、分析、評(píng)價(jià),篩選出抗恐懼藥物藥效的評(píng)價(jià)指標(biāo),以期為抗恐懼藥物藥效評(píng)價(jià)指標(biāo)體系的建立提供資料。 方法:64只健康雄性Wistar大鼠隨機(jī)分為恐懼應(yīng)激組及對(duì)照組,每組32只。自由攝食飲水飼養(yǎng)10天后,第11天起恐懼模型組每日給予2s噪音+3s足底電流刺激,電流強(qiáng)度為1mA,間隔1min,共30次;對(duì)照組每日只給予2s噪音,無足底電流刺激,間隔1min,共30次。第14天攝像記錄兩組大鼠5min噪音之后6～30min內(nèi)行為變化,評(píng)定模型是否建立。自模型建立后分別于第1、2、3、4周每周周中(第18、25、32、39天)對(duì)兩組大鼠進(jìn)行一般狀態(tài)、應(yīng)激行為反應(yīng)(凍結(jié)時(shí)間、自發(fā)活動(dòng)等)和生理反應(yīng)(血清皮質(zhì)酮COR)以及腦損傷(神經(jīng)元烯醇化酶NSE、海馬形態(tài)學(xué))的觀察和測(cè)定。 結(jié)果:1.恐懼模型組大鼠的凍結(jié)行為學(xué)得分顯著高于空白對(duì)照組(P 0.01),表明建立條件恐懼應(yīng)激模型有效。2.恐懼模型組大鼠同對(duì)照組相比,在4周各不同時(shí)間段內(nèi)均表現(xiàn)出神態(tài)疲倦、毛發(fā)蓬亂無光澤、飲食量減少、大便稀溏現(xiàn)象;兩組大鼠體重均呈增長(zhǎng)態(tài)勢(shì),恐懼模型組體重增長(zhǎng)較對(duì)照組緩慢,第2周(P 0.05)、第3周(P 0.05)、第4周(P 0.01)兩組大鼠體重比較均差異顯著。3.恐懼模型組大鼠同對(duì)照組相比,在4周各不同時(shí)間段內(nèi)均表現(xiàn)出易激惹、廝打行為多、活動(dòng)減少、扎堆懶散等現(xiàn)象;兩組大鼠自發(fā)活動(dòng)比較,恐懼模型組休息時(shí)間在第1周(P 0.05)、第2周(P 0.01)、第3周(P 0.05)、第4周(P 0.05)均顯著多于對(duì)照組。4.兩組大鼠血清皮質(zhì)酮含量比較,恐懼模型組血清皮質(zhì)酮濃度在第1周(P 0.05)、第2周(P 0.01)、第3周(P 0.05)、第4周(P 0.05)均顯著高于對(duì)照組。5.兩組大鼠血清NSE含量比較,恐懼模型組血清NSE濃度在第1周(P 0.05)顯著高于對(duì)照組,其余各周均無統(tǒng)計(jì)學(xué)差異;對(duì)大鼠海馬部位切片進(jìn)行HE染色,結(jié)果顯示對(duì)照組大鼠海馬CA1及CA3區(qū)錐體細(xì)胞與齒狀回(DG)顆粒細(xì)胞的形態(tài)正常,細(xì)胞排列整齊、層次緊密,細(xì)胞完整,邊緣清晰,核仁清晰可見;恐懼應(yīng)激組大鼠應(yīng)激第1周、第2周海馬CA1、CA3區(qū)、齒狀回(DG)細(xì)胞體積腫脹、細(xì)胞淡染、細(xì)胞排列稍顯稀疏,第3周細(xì)胞萎縮,細(xì)胞間隙增大,細(xì)胞層次變稀、中斷,第4周,細(xì)胞形態(tài)不規(guī)則,細(xì)胞數(shù)量減少,排列疏松不齊,大量細(xì)胞壞死,出現(xiàn)細(xì)胞核固縮、破裂等現(xiàn)象。 結(jié)論:本研究結(jié)果表明,經(jīng)過改良的Takeuchi法可以建立條件恐懼應(yīng)激模型,條件恐懼應(yīng)激可引起大鼠急、慢性恐懼應(yīng)激,影響大鼠的生理反應(yīng)和行為反應(yīng),并引起大鼠腦損傷。研究結(jié)果可為恐懼對(duì)應(yīng)激反應(yīng)的影響及腦損傷效應(yīng)提供依據(jù),為抗恐懼藥物藥效評(píng)價(jià)指標(biāo)體系的建立提供資料。
[Abstract]:Objective: To establish a conditional fear stress model, to comprehensively detect, analyze and evaluate the related indexes of stress and brain injury in rats under the condition of condition and fear stress, and to select the evaluation index of the drug effect of the anti-fear drugs. So as to provide data for the establishment of the evaluation index system for the drug effect of the anti-fear drugs. Methods:64 healthy male Wistar rats were randomly divided into two groups: the fear stress group and the control group. Only. After 10 days of free-feeding drinking water, the 11-day fear model group was given a 2-s noise plus 3 s foot-foot current stimulation every day, the current intensity was 1 mA, the interval was 1 min, total 30 times, the control group only given 2 s of noise every day, no foot-foot current stimulation, interval of 1 min, total of 30 Sub. 14-day imaging and recording the behavior change of the two groups of rats at 5 min after 5 min of noise, and whether the model was built or not General status, stress behavior (freezing time, spontaneous activity, etc.) and physiological response (serum corticosterone COR) and brain injury (neuron enolase NS) were performed on the first, second, third, and fourth week (day 18,25,32,39 days) after the model was established. E. Observation and measurement of the morphology of the hippocampus knot Results:1. The frozen behavior score of the rats with the fear model group was significantly higher than that of the blank control group (P 0.01). 2. Compared with the control group, the model group of the model group showed that the body weight of the two groups was increased, and the body weight of the model group was higher than that of the control group. The group was slow, the second week (P 0.05), the third week (P 0.05), and the fourth week (P 0.01). .3. Compared with the control group, the rats of the model group of the fear model showed the phenomena of excitability, more action, less activity, and idleness of the group in different time periods, and the rest time of the fear model group was at the first week (P 0.05) and the second week (P 0). 01), Week 3 (P 0.05), Week 4 (P 0.05), significantly more than control The serum corticosterone levels in the two groups were significantly higher than those in the control group in the first week (P 0.05), the second week (P 0.01), the third week (P 0.05) and the fourth week (P 0.05). The serum NSE in the two groups was significantly higher than that in the control group at week 1 (P 0.05), and there was no statistical difference in the other week. E. The results showed that the morphology of the pyramidal cells and the dentate gyrus (DG) of the hippocampal CA1 and CA3 regions in the control group were normal, the cells were orderly, the layers were close, the cells were intact, the edges were clear, the nucleoli were clearly visible, and the rats with the fear stress group were stressed in the first week and the second week in the hippocampus CA1 and C. In the A3 region, the volume of the dentate gyrus (DG) cells is swollen, the cells are light-stained, the cell arrangement is slightly sparse, the cells in the third week atrophy, the cell gap is increased, the cell level is thin, the interruption, the fourth week, the cell morphology is irregular, the number of cells is reduced, the arrangement is not uniform, and a large amount of fine particles The necrosis of the cell, the presence of a cell nucleus, a contraction, a rupture, Conclusion: The results of this study show that the modified Takeuchi method can establish a condition fear stress model, which can cause acute and chronic fear stress in rats, which can affect the physiological response and behavior of the rats, and cause The results of the study can provide the basis for the effect of the fear on the stress response and the effect of the brain injury.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R-332

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