發(fā)布時(shí)間：2019-04-03 08:21

【摘要】：目的:研究表明環(huán)氧合酶-2(COX-2)參與學(xué)習(xí)記憶過(guò)程;COX-2抑制劑帕瑞昔布鈉可改善病理?xiàng)l件下學(xué)習(xí)記憶功能損傷,但其對(duì)正常生理狀態(tài)下學(xué)習(xí)記憶功能的影響仍不清楚。此外,帕瑞昔布鈉對(duì)焦慮和抑郁行為的影響也有待闡明。本研究檢測(cè)了慢性帕瑞昔布鈉處理對(duì)小鼠學(xué)習(xí)記憶、焦慮及抑郁行為的影響;同時(shí)檢測(cè)了慢性帕瑞昔布鈉對(duì)小鼠杏仁核及海馬突觸素表達(dá)水平的影響以期對(duì)其可能的神經(jīng)機(jī)制進(jìn)行初步探討。方法:1.慢性帕瑞昔布鈉處理:ICR小鼠腹腔注射帕瑞昔布鈉(2.5,5.0和10 mg/kg),連續(xù)注射28天;對(duì)照組小鼠注射等體積的生理鹽水。2.新穎物體識(shí)別(NOR)測(cè)試:帕瑞昔布鈉連續(xù)注射8天后行新穎物體識(shí)別測(cè)試。在短時(shí)程N(yùn)OR測(cè)試中,訓(xùn)練階段與檢測(cè)階段的時(shí)間間隔為4h;在長(zhǎng)時(shí)程N(yùn)OR測(cè)試中,訓(xùn)練階段與檢測(cè)階段的時(shí)間間隔為24h。記錄分析小鼠在訓(xùn)練階段對(duì)兩物體總的探究時(shí)間及在檢測(cè)階段的辨別指數(shù)。3.Y迷宮測(cè)試:帕瑞昔布鈉連續(xù)注射11天后行Y迷宮測(cè)試,記錄小鼠在8分鐘內(nèi)總?cè)氡鄞螖?shù)及入臂交替比率。4.高架十字迷宮測(cè)試:帕瑞昔布鈉連續(xù)注射17天后行高架十字迷宮測(cè)試,記錄分析小鼠在5分鐘內(nèi)閉臂入臂次數(shù)、開(kāi)臂入臂次數(shù)百分比及開(kāi)臂停留時(shí)間百分比。5.懸尾測(cè)試:帕瑞昔布鈉連續(xù)注射18天后行懸尾測(cè)試,記錄小鼠在5分鐘內(nèi)的不動(dòng)時(shí)間。6.強(qiáng)迫游泳測(cè)試:帕瑞昔布鈉連續(xù)注射19天后行強(qiáng)迫游泳測(cè),記錄小鼠在5分鐘內(nèi)的不動(dòng)時(shí)間。7.Western blot檢測(cè):行為學(xué)測(cè)試完成后,斷頭取腦,分離海馬和杏仁核。Western blot檢測(cè)海馬和杏仁核突觸素表達(dá)水平。結(jié)果:1.在短時(shí)程與長(zhǎng)時(shí)程N(yùn)OR測(cè)試中,四組小鼠在訓(xùn)練階段對(duì)兩物體總探究時(shí)間均無(wú)顯著性組間差異;在檢測(cè)階段,10 mg/kg帕瑞昔布鈉組小鼠辨別指數(shù)均顯著性高于生理鹽水組。2.在Y迷宮測(cè)試中,四組小鼠總?cè)氡鄞螖?shù)無(wú)顯著性組間差異;10 mg/kg帕瑞昔布鈉組小鼠入臂交替比率顯著性高于生理鹽水組。3.在高架十字迷宮測(cè)試中,四組小鼠閉臂入臂次數(shù)無(wú)顯著性組間差異;5與10 mg/kg帕瑞昔布鈉組小鼠開(kāi)臂入臂次數(shù)百分比及開(kāi)臂停留時(shí)間百分比顯著性高于生理鹽水組。4.在懸尾測(cè)試中,四組小鼠的不動(dòng)時(shí)間無(wú)顯著性組間差異。5.在強(qiáng)迫游泳測(cè)試中,四組小鼠的不動(dòng)時(shí)間無(wú)顯著性組間差異。6.帕瑞昔布鈉(10mg/kg)組小鼠海馬和杏仁核內(nèi)的突觸素表達(dá)水平較生理鹽水組顯著升高。結(jié)論:1.慢性帕瑞昔布鈉處理可增強(qiáng)小鼠學(xué)習(xí)和記憶功能,其機(jī)制可能與帕瑞昔布鈉上調(diào)海馬和杏仁核內(nèi)的突觸素表達(dá)水平有關(guān)。2.慢性帕瑞昔布鈉處理可改善小鼠的焦慮行為,但對(duì)小鼠抑郁行為無(wú)影響。
[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.
【學(xué)位授予單位】：南華大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R614

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