大鼠恐惧应激模型的建立与评价指标筛选
发布时间：2019-06-26 14:37
【摘要】：目的:建立条件恐惧应激模型,对条件恐惧应激条件下大鼠应激反应和脑损伤相关指标进行综合的检测、分析、评价,筛选出抗恐惧药物药效的评价指标,以期为抗恐惧药物药效评价指标体系的建立提供资料。 方法:64只健康雄性Wistar大鼠随机分为恐惧应激组及对照组,每组32只。自由摄食饮水饲养10天后,第11天起恐惧模型组每日给予2s噪音+3s足底电流刺激,电流强度为1mA,间隔1min,共30次;对照组每日只给予2s噪音,无足底电流刺激,间隔1min,共30次。第14天摄像记录两组大鼠5min噪音之后6～30min内行为变化,评定模型是否建立。自模型建立后分别于第1、2、3、4周每周周中(第18、25、32、39天)对两组大鼠进行一般状态、应激行为反应(冻结时间、自发活动等)和生理反应(血清皮质酮COR)以及脑损伤(神经元烯醇化酶NSE、海马形态学)的观察和测定。 结果:1.恐惧模型组大鼠的冻结行为学得分显著高于空白对照组(P 0.01),表明建立条件恐惧应激模型有效。2.恐惧模型组大鼠同对照组相比,在4周各不同时间段内均表现出神态疲倦、毛发蓬乱无光泽、饮食量减少、大便稀溏现象;两组大鼠体重均呈增长态势,恐惧模型组体重增长较对照组缓慢,第2周(P 0.05)、第3周(P 0.05)、第4周(P 0.01)两组大鼠体重比较均差异显著。3.恐惧模型组大鼠同对照组相比,在4周各不同时间段内均表现出易激惹、厮打行为多、活动减少、扎堆懒散等现象;两组大鼠自发活动比较,恐惧模型组休息时间在第1周(P 0.05)、第2周(P 0.01)、第3周(P 0.05)、第4周(P 0.05)均显著多于对照组。4.两组大鼠血清皮质酮含量比较,恐惧模型组血清皮质酮浓度在第1周(P 0.05)、第2周(P 0.01)、第3周(P 0.05)、第4周(P 0.05)均显著高于对照组。5.两组大鼠血清NSE含量比较,恐惧模型组血清NSE浓度在第1周(P 0.05)显著高于对照组,其余各周均无统计学差异;对大鼠海马部位切片进行HE染色,结果显示对照组大鼠海马CA1及CA3区锥体细胞与齿状回(DG)颗粒细胞的形态正常,细胞排列整齐、层次紧密,细胞完整,边缘清晰,核仁清晰可见;恐惧应激组大鼠应激第1周、第2周海马CA1、CA3区、齿状回(DG)细胞体积肿胀、细胞淡染、细胞排列稍显稀疏,第3周细胞萎缩,细胞间隙增大,细胞层次变稀、中断,第4周,细胞形态不规则,细胞数量减少,排列疏松不齐,大量细胞坏死,出现细胞核固缩、破裂等现象。 结论:本研究结果表明,经过改良的Takeuchi法可以建立条件恐惧应激模型,条件恐惧应激可引起大鼠急、慢性恐惧应激,影响大鼠的生理反应和行为反应,并引起大鼠脑损伤。研究结果可为恐惧对应激反应的影响及脑损伤效应提供依据,为抗恐惧药物药效评价指标体系的建立提供资料。
[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.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R-332
本文编号：2506261
[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.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R-332
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