本文選題：酰米菲肽 + 抗抑郁�。� 參考：《中國人民解放軍醫(yī)學院》2014年碩士論文

【摘要】：目的：評價酰米菲肽（代號：XMT）的抗抑郁作用，初步研究其可能的作用機制。 方法：1、采用小鼠行為絕望模型（小鼠懸尾實驗、小鼠強迫游泳實驗）和大鼠慢性不可預測性溫和應激（CUMS）抑郁模型評價酰米菲肽的抗抑郁作用。2、采用藥物誘發(fā)行為藥理學模型（5-羥色氨酸誘導甩頭實驗、育亨賓毒性增強實驗）和高效液相色譜-電化學檢測法（HPLC-ECD）測定大鼠大腦前額皮層單胺神經遞質及其代謝產物的含量，從中樞單胺系統(tǒng)水平研究酰米菲肽的抗抑郁作用機制。3、采用酶聯(lián)免疫法（ELISA）測定大鼠血清促腎上腺皮質激素（ACTH）和皮質酮（CORT）含量，從下丘腦-垂體-腎上腺素（HPA）軸水平探究酰米菲肽的抗抑郁作用機制。4、采用Morris水迷宮實驗評價酰米菲肽對大鼠空間學習記憶能力的影響。結果：1、懸尾實驗和強迫游泳實驗中，酰米菲肽可分別顯著縮短小鼠的懸尾和游泳不動時間；在有效劑量范圍內，酰米菲肽對小鼠的自發(fā)活動沒有影響，排除了中樞興奮劑對實驗結果產生假陽性的干擾。以上實驗結果表明，酰米菲肽在小鼠行為絕望模型中具有一定的抗抑郁作用。2、酰米菲肽可顯著提高CUMS抑郁模型大鼠的糖水偏嗜度、曠場實驗的水平和垂直運動得分、并可顯著改善抑郁模型大鼠體重增長減慢的現(xiàn)象。以上實驗結果表明，酰米菲肽可顯著緩解CUMS抑郁模型大鼠的快感缺失、活動量減少、興趣缺乏、體重增加緩慢等抑郁樣行為，具有良好的抗抑郁作用。3、5-HTP誘導小鼠甩頭實驗中，酰米菲肽可顯著減少5-HTP誘導的甩頭行為，而在育亨賓毒性增強實驗中，酰米菲肽對育亨賓的毒性沒有明顯增強作用，提示酰米菲肽的抗抑郁作用可能與中樞5-HT能系統(tǒng)相關。4、酰米菲肽可不同程度提高CUMS抑郁模型大鼠前額皮層區(qū)5-HT、DA含量，并且顯著提高前額皮層區(qū)5-HT/5-HIAA和DA/DOPAC的比值，，降低5-HT和DA在腦內的轉化率，提示酰米菲肽的抗抑郁作用可能與抑制單胺氧化酶相關。5、酰米菲肽可顯著降低CUMS抑郁模型大鼠血清ACTH和CORT水平，提示酰米菲肽的抗抑郁作用可能與抑制HPA軸功能亢進相關。6、Morris水迷宮實驗中，酰米菲肽可明顯提高大鼠穿越平臺所在位置的次數(shù)、平臺所在象限停留的時間和移動路程，表明酰米菲肽具有改善CUMS造成大鼠認知功能損傷的作用。結論：1、酰米菲肽在小鼠行為絕望模型和大鼠CUMS抑郁模型中具有一定的抗抑郁作用。2、酰米菲肽抗抑郁作用機制可能與中樞5-HT能系統(tǒng)、HPA軸等多種途徑相關。3、酰米菲肽可改善CUMS抑郁模型大鼠的空間學習記憶能力障礙。
[Abstract]:Aim: to evaluate the antidepressant effect of acyl miffy peptide (XMTA) and to study its possible mechanism. Methods: 1. The mouse behavioral despair model (mouse tail suspension test) was used. The antidepressant effect of acyl miffy peptide was evaluated in rats with chronic unpredictability mild stress (CUMS) and forced swimming in mice. The pharmacological model of drug-induced behavior was used to induce head flick induced by 5-hydroxytryptophan. The contents of monoamine neurotransmitters and their metabolites in the prefrontal cortex of rats were determined by high performance liquid chromatography-electrochemical detection (HPLC-ECD). The antidepressant mechanism of acyl miffy peptide was studied at the level of central monoamine system. The levels of serum adrenocorticotropic hormone (ACTH) and corticosterone (Cort) were measured by enzyme linked immunosorbent assay (Elisa). The antidepressant mechanism of acyl miffy peptide was investigated by using hypothalamus-pituitary-adrenaline (HPA) axis. The effects of acyl miffy peptide on spatial learning and memory in rats were evaluated by Morris water maze test. Results: in the tail suspension test and forced swimming test, Acyl miffy peptide significantly shortened the tail suspension and swimming immobility time of mice, but in the effective dose range, the acyl miffy peptide had no effect on the spontaneous activity of mice. The effect of central stimulant on the false positive results was excluded. The results showed that Acyl miffy peptide had a certain antidepressant effect in the behavioral despair model of mice. Acyl miffy peptide could significantly increase the degree of preference of sugar and water and the scores of horizontal and vertical motion of open field test in CUMS depression model rats. And can significantly improve the depression model rats weight growth slow down phenomenon. The results showed that Acyl miffy peptide could significantly alleviate the depression-like behaviors such as loss of pleasure, decreased activity, lack of interest, slow weight gain and so on, and had a good antidepressant effect. Acyl miffy peptide could significantly reduce the head flick behavior induced by 5-HTP, but in yohimbine toxicity enhancement test, the toxicity of acyl miffy peptide to yohimbine was not significantly enhanced. It is suggested that the antidepressant effect of acyl miffy peptide may be related to the central 5-HT energy system. Acyl miffy peptide can increase the content of 5-HTDA in the prefrontal cortex and the ratio of 5-HT/5-HIAA to DA/DOPAC in the prefrontal cortex of CUMS depression model rats. The decrease of the conversion rate of 5-HT and DA in brain suggests that the antidepressant effect of acyl miffy peptide may be related to the inhibition of monoamine oxidase. Acyl miffy peptide can significantly reduce the levels of serum ACTH and CORT in rats with CUMS depression. It is suggested that the antidepressant effect of acyl miffy peptide may be related to the inhibition of hyperfunction of HPA axis. In the Morris water maze experiment, the number of times of crossing the platform, the time of staying in the quadrant and the distance of movement of the platform were significantly increased. The results suggest that the acyl miffy peptide can improve the cognitive impairment induced by CUMS in rats. Conclusion: 1, Acyl miffy peptide has antidepressant effect in mouse behavioral despair model and rat CUMS depression model. The antidepressant mechanism of acyl miffy peptide may be related to several pathways, such as central 5-HT energy system, CUMS axis, etc., and acyl miffy peptide may be related to the antidepressant effect of Acyl miffy peptide. It can improve the ability of spatial learning and memory in CUMS depression model rats.
【學位授予單位】：中國人民解放軍醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R96

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