本文選題：苯丙胺　切入點(diǎn)：腦　出處：《暨南大學(xué)》2010年碩士論文　論文類型：學(xué)位論文

【摘要】： 目的： 探討二氫嘧啶酶相關(guān)蛋白2(DRP-2)在苯丙胺致小鼠腦損傷中的變化和機(jī)制。 方法： 將60只健康雄性C57BL／6小鼠隨機(jī)分為：正常對(duì)照組、生理鹽水組和苯丙胺組。苯丙胺組又分為1 d、7d、14d和28 d四個(gè)組,腹腔注射苯丙胺2 mg/kg/d。生理鹽水組僅設(shè)28 d組,等量生理鹽水注射。正常組不予任何處理。建模期間進(jìn)行小鼠自主行為活動(dòng)測(cè)試,電腦記錄運(yùn)動(dòng)總路程、運(yùn)動(dòng)總時(shí)間、平均速度、最大速度、慢速運(yùn)動(dòng)時(shí)間、慢速運(yùn)動(dòng)時(shí)間／總時(shí)間、快速運(yùn)動(dòng)時(shí)間和快速運(yùn)動(dòng)時(shí)間／總時(shí)間等指標(biāo),檢測(cè)動(dòng)物的自主活動(dòng)度。動(dòng)物模型建立完成后,按照實(shí)驗(yàn)所需方法取材,采用銀染(Nauta)法、免疫組織化學(xué)法及Western blotting法等觀察苯丙胺對(duì)小鼠腦的毒性損害作用以及對(duì)DRP-2及其上游AKT/GSK-3β信號(hào)通路的影響。 結(jié)果： 1.自主行為學(xué)檢測(cè)：用藥前各組小鼠的最大速度、平均速度、運(yùn)動(dòng)總路程、快速運(yùn)動(dòng)時(shí)間／總時(shí)間均沒有顯著差異(P0.05)。用藥后,苯丙胺7 d、14 d、28 d組的運(yùn)動(dòng)總路程、平均速度、快速運(yùn)動(dòng)時(shí)間／總時(shí)間／最大運(yùn)動(dòng)速度比正常對(duì)照組和生理鹽水組增加(P0.05),而慢速運(yùn)動(dòng)時(shí)間／總時(shí)間在各組間沒有顯著差異(P0.05)。 2.潰變神經(jīng)纖維及其終末的銀染結(jié)果：Nauta法染色顯示苯丙胺14 d和28 d組紋狀體內(nèi)可見變性神經(jīng)纖維呈黑色,正常組和生理鹽水組均未發(fā)現(xiàn)變性的神經(jīng)纖維。 3.多巴胺(DA)能神經(jīng)元及其纖維的變化：苯丙胺28 d組小鼠黑質(zhì)致密部的DA能神經(jīng)元數(shù)比其它各組均減少(P0.05)。苯丙胺1d組和生理鹽水組蒼白球區(qū)DA神經(jīng)纖維密度比正常組增加(P0.05),但隨著用藥時(shí)間的延長(zhǎng),苯丙胺14d和28 d組蒼白球區(qū)的DA神經(jīng)纖維密度比正常對(duì)照組和生理鹽水組降低(P0.05)。 4.DRP-2及其蛋白激酶B／糖原合成激酶3p(AKT/GSK-3β)信號(hào)通路的變化：苯丙胺組紋狀體內(nèi)DRP-2的表達(dá)較生理鹽水組和正常組明顯減少(P0.05),而P-DRP-2的表達(dá)苯丙胺1d組與正常組無明顯變化(P0.05),苯丙胺7d、14d組和生理鹽水組較正常組增加(P0.05)。苯丙胺28d組AKT的表達(dá)較正常組和生理鹽水組減少(P0.05)。苯丙胺7d、14d和28d組GSK-3β的表達(dá)比正常組增多(P0.05)。 結(jié)論： 1.苯丙胺可引起小鼠自主活動(dòng)性增加。 2.長(zhǎng)期使用苯丙胺可導(dǎo)致起小鼠紋狀體神經(jīng)纖維變性。 3.長(zhǎng)期使用苯丙胺可導(dǎo)致起小鼠黑質(zhì)致密部的DA能神經(jīng)元數(shù)目減少,以及蒼白球區(qū)DA神經(jīng)纖維密度的降低。 4.使用苯丙胺可引起小鼠紋狀體P-DRP-2的增加以及DRP-2的減少,其機(jī)理與抑制AKT/GSK-3β信號(hào)通路的有密切關(guān)系。
[Abstract]:Objective:. To investigate the changes and mechanism of dihydropyrimidinase-associated protein 2DRP-2 in brain injury induced by amphetamine in mice. Methods:. Sixty healthy male C57BL / 6 mice were randomly divided into normal control group, saline group and amphetamine group. The normal group did not receive any treatment. During the modeling period, the mice were tested for autonomous behavior, and the total distance, time, average speed, maximum speed, slow motion time were recorded by computer. The indexes of slow motion time / total time, fast motion time and fast motion time / total time were used to detect the autonomous activity of animals. After the establishment of the animal model, the materials were obtained according to the method needed in the experiment, and the silver staining Nauta method was used. Immunohistochemical method and Western blotting method were used to observe the toxic effects of amphetamine on the brain of mice and the effects on DRP-2 and its upstream AKT/GSK-3 尾 signaling pathway. Results:. 1. Detection of autonomic behavior: there was no significant difference in maximal velocity, average speed, total distance, time / total time of rapid exercise in each group before treatment. After treatment, the total distance and average speed of the rats in the group of amphetamine 7 days and 14 days and 28 days after treatment were not significantly different. The rapid exercise time / total time / maximum exercise velocity increased P0.05 compared with normal control group and normal saline group, but there was no significant difference in slow exercise time / total time between groups. 2. The results of silver staining of degenerated nerve fibers and their terminals showed that denatured nerve fibers were black in striatum of 14 d and 28 d groups of amphetamine, but no denatured nerve fibers were found in normal group and normal saline group. 3. Changes of dopaminergic neurons and their fibers: the number of DA neurons in the substantia nigra of the rats in the 28 d group was lower than that in the other groups (P 0.05), and the density ratio of DA fibers in the globus pallidus was positive in the 1 d group and the saline group. In the normal group, P0.05 was increased, but with the prolongation of the medication time, The density of DA nerve fibers in the globus pallidus of 14 d and 28 d group was lower than that of normal control group and normal saline group. 4. The changes of signal pathway of DRP-2 and its protein kinase B / glycogen synthesis kinase 3pAK / GSK-3 尾: the expression of DRP-2 in striatum of amphetamine group was significantly lower than that of normal saline group and normal group, but the expression of P-DRP-2 was not significantly changed in phenylalanine 1 day group and normal group (P0.05). Compared with the control group, the expression of AKT in the amphetamine 28d group was lower than that in the normal saline group (P 0.05). The expression of GSK-3 尾 in the phenylalanine group was significantly higher than that in the control group on day 14 and 28. The expression of GSK-3 尾 in the control group was significantly higher than that in the control group (P 0.05). Conclusion:. 1. Amphetamine induced increased autonomous activity in mice. 2. Long-term use of amphetamine can lead to degeneration of striatum nerve fibers in mice. 3. The number of DA neurons in the substantia nigra and the density of DA nerve fibers in the ganglia pallidus were decreased after long-term use of amphetamine. 4. The increase of P-DRP-2 and the decrease of DRP-2 in the striatum of mice induced by amphetamine were closely related to the inhibition of AKT/GSK-3 尾 signaling pathway.
【學(xué)位授予單位】：暨南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類號(hào)】：R363

【參考文獻(xiàn)】

相關(guān)期刊論文 前7條

1 劉鐵橋,郝偉;苯丙胺類興奮劑概介[J];國外醫(yī)學(xué).精神病學(xué)分冊(cè);2001年03期

2 趙妍君;伏膈核神經(jīng)元的分型及其形態(tài)和生理學(xué)特征[J];國外醫(yī)學(xué)(精神病學(xué)分冊(cè));2002年02期

3 張秀娟,徐滿英;伏隔核功能的研究進(jìn)展[J];哈爾濱醫(yī)科大學(xué)學(xué)報(bào);2002年04期

4 周軍蘭,梁建輝;甲基苯丙胺神經(jīng)毒性機(jī)制的研究進(jìn)展[J];中國藥理學(xué)通報(bào);2003年05期

5 高小平;苯丙胺類毒品將成為21世紀(jì)泛濫最廣泛的毒品[J];中國藥物依賴性雜志;2002年01期

6 郝海靜;劉志民;;2005年聯(lián)合國毒品及犯罪年度報(bào)告內(nèi)容摘要[J];中國藥物依賴性雜志;2006年02期

7 姜佐寧;跨世紀(jì)的苯丙胺類興奮劑:流行趨向與新的危害[J];中國藥物依賴性雜志;1999年03期

，

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