慢性帕瑞昔布钠处理对小鼠学习记忆、焦虑及抑郁行为的影响

发布时间：2019-04-03 08:21

【摘要】：目的:研究表明环氧合酶-2(COX-2)参与学习记忆过程;COX-2抑制剂帕瑞昔布钠可改善病理条件下学习记忆功能损伤,但其对正常生理状态下学习记忆功能的影响仍不清楚。此外,帕瑞昔布钠对焦虑和抑郁行为的影响也有待阐明。本研究检测了慢性帕瑞昔布钠处理对小鼠学习记忆、焦虑及抑郁行为的影响;同时检测了慢性帕瑞昔布钠对小鼠杏仁核及海马突触素表达水平的影响以期对其可能的神经机制进行初步探讨。方法:1.慢性帕瑞昔布钠处理:ICR小鼠腹腔注射帕瑞昔布钠(2.5,5.0和10 mg/kg),连续注射28天;对照组小鼠注射等体积的生理盐水。2.新颖物体识别(NOR)测试:帕瑞昔布钠连续注射8天后行新颖物体识别测试。在短时程NOR测试中,训练阶段与检测阶段的时间间隔为4h;在长时程NOR测试中,训练阶段与检测阶段的时间间隔为24h。记录分析小鼠在训练阶段对两物体总的探究时间及在检测阶段的辨别指数。3.Y迷宫测试:帕瑞昔布钠连续注射11天后行Y迷宫测试,记录小鼠在8分钟内总入臂次数及入臂交替比率。4.高架十字迷宫测试:帕瑞昔布钠连续注射17天后行高架十字迷宫测试,记录分析小鼠在5分钟内闭臂入臂次数、开臂入臂次数百分比及开臂停留时间百分比。5.悬尾测试:帕瑞昔布钠连续注射18天后行悬尾测试,记录小鼠在5分钟内的不动时间。6.强迫游泳测试:帕瑞昔布钠连续注射19天后行强迫游泳测,记录小鼠在5分钟内的不动时间。7.Western blot检测:行为学测试完成后,断头取脑,分离海马和杏仁核。Western blot检测海马和杏仁核突触素表达水平。结果:1.在短时程与长时程NOR测试中,四组小鼠在训练阶段对两物体总探究时间均无显著性组间差异;在检测阶段,10 mg/kg帕瑞昔布钠组小鼠辨别指数均显著性高于生理盐水组。2.在Y迷宫测试中,四组小鼠总入臂次数无显著性组间差异;10 mg/kg帕瑞昔布钠组小鼠入臂交替比率显著性高于生理盐水组。3.在高架十字迷宫测试中,四组小鼠闭臂入臂次数无显著性组间差异;5与10 mg/kg帕瑞昔布钠组小鼠开臂入臂次数百分比及开臂停留时间百分比显著性高于生理盐水组。4.在悬尾测试中,四组小鼠的不动时间无显著性组间差异。5.在强迫游泳测试中,四组小鼠的不动时间无显著性组间差异。6.帕瑞昔布钠(10mg/kg)组小鼠海马和杏仁核内的突触素表达水平较生理盐水组显著升高。结论:1.慢性帕瑞昔布钠处理可增强小鼠学习和记忆功能,其机制可能与帕瑞昔布钠上调海马和杏仁核内的突触素表达水平有关。2.慢性帕瑞昔布钠处理可改善小鼠的焦虑行为,但对小鼠抑郁行为无影响。
[Abstract]:Objective: to investigate the role of cyclooxygenase-2 (COX-2) in learning and memory. Parracoxib sodium, an inhibitor of COX-2, can improve learning and memory impairment under pathological conditions, but its effect on learning and memory function under normal physiological condition is still unclear. In addition, the effect of paracoxib sodium on anxiety and depression behavior remains to be clarified. In this study, the effects of chronic paracoxib sodium treatment on learning and memory, anxiety and depression in mice were investigated. The effects of chronic paracoxib sodium on the expression of synaptophysin in the amygdala and hippocampus of mice were examined in order to explore the possible neuromechanism. Methods: 1. Chronic paracoxib sodium treatment: ICR mice were intraperitoneally injected with paracoxib sodium (2.5, 5.0 and 10 mg/kg) for 28 days, and control mice were injected with equal volume of saline. Novel object recognition (NOR) test: after 8 days of continuous injection of Parracoxib sodium, a novel object recognition test was performed. In the short-term NOR test, the time interval between the training phase and the detection phase is 4 hours, and in the long-term NOR test, the time interval between the training phase and the detection phase is 24 hours. The total inquiring time of the two bodies in the training phase and the discrimination index in the test phase were recorded and analyzed. 3. Y maze test: after 11 days of continuous injection of Parracoxib sodium, the Y labyrinth test was performed. The total number of entrances and the ratio of arm alternation in 8 minutes were recorded in the mice. 4. Elevated cross labyrinth test: after 17 days of continuous injection of Parracoxib sodium, the mice were recorded and analyzed the number of closed arms in 5 minutes, the percentage of open arm entry times and the percentage of open arm stay time. 5. Tail suspension test: after 18 days of continuous injection of Parracoxib sodium, the tail suspension test was performed to record the immobility time of mice within 5 minutes. 6. Forced swimming test: after 19 days of continuous injection of Parracoxib sodium, forced swimming test was performed to record the immobility time of the mice within 5 minutes. 7. Western blot test: after the behavioral test was completed, the head was decapitated and the brain was removed. The expression of synaptophysin in hippocampus and amygdaloid nucleus was detected by. Western blot isolation from hippocampus and amygdala. Results: 1. In the short-term and long-term NOR tests, there was no significant difference in the total inquiry time of the two objects between the four groups in the training stage; in the detection stage, the discrimination index of the 10-mg/kg Parracoxib sodium group was significantly higher than that of the physiological saline group. 2. In the Y labyrinth test, there was no significant difference in the total frequency of the arm between the four groups, and the ratio of the arm alternation in the 10 mg/kg paracoxib sodium group was significantly higher than that in the physiological saline group. 3. In the elevated maze test, there was no significant difference in the number of closed arms between the four groups, 5 and 10 mg/kg paracoxib sodium group were significantly higher than the physiological saline group in the percentage of open arm entry times and the percentage of open arm residence time. 4. The results showed that there was no significant difference between the four groups in the number of open arm entrances and the percentage of open arm residence time. In the tail suspension test, there was no significant difference in immobility time among the four groups. 5. In the forced swimming test, there was no significant difference in the immobility time between the four groups. 6. The expression level of synaptophysin in hippocampus and amygdala in 10mg/kg group was significantly higher than that in saline group. Conclusions: 1. Chronic paracoxib sodium treatment can enhance the learning and memory function of mice, and its mechanism may be related to the up-regulation of synaptophysin expression in hippocampus and amygdala by Parracoxib sodium. 2. Chronic paracoxib sodium treatment could improve the anxiety behavior of mice, but had no effect on the depression behavior of mice.
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R614

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