本文選題：甲基苯丙胺　切入點(diǎn)：大鼠依賴模型　出處：《昆明醫(yī)科大學(xué)》2013年碩士論文

【摘要】：目的：建立甲基苯丙胺(MA)依賴大鼠模型,觀察MA依賴鼠伏隔核和側(cè)腦室注射膠質(zhì)細(xì)胞源性營(yíng)養(yǎng)因子(GDNF)后伏隔核多巴胺D2受體(DRD2)和多巴胺轉(zhuǎn)運(yùn)體(DAT)的變化,探討外源性GDNF干預(yù)對(duì)甲基苯丙胺依賴鼠伏隔核機(jī)能代謝變化的影響。方法：SD大鼠160只,隨機(jī)分為對(duì)照組、依賴一周、四周及八周組,建立不同依賴時(shí)間段的大鼠模型,三個(gè)實(shí)驗(yàn)組又分別分為5個(gè)亞組：?jiǎn)渭僊A依賴組、MA依賴+假手術(shù)組、MA依賴+蒸餾水組、MA依賴+GDNF低劑量干預(yù)組及MA依賴+GDNF高劑量干預(yù)組。應(yīng)用免疫組化技術(shù)、原位雜交技術(shù)、蛋白質(zhì)免疫印跡技術(shù)和實(shí)時(shí)定量PCR技術(shù)檢測(cè)伏隔核DRD2、DAT蛋白質(zhì)及其mRNA的變化。結(jié)果：1.與對(duì)照組比較,三個(gè)單純甲基苯丙胺依賴組的條件性位置偏愛(ài)實(shí)驗(yàn)均有顯著性差異,甲基苯丙胺依賴大鼠模型成功建立。2.與對(duì)照組比較,三個(gè)實(shí)驗(yàn)組內(nèi)不同亞組,伏隔核DRD2、DAT表達(dá)均有變化。DRD2及其mRNA在單純MA依賴組、MA依賴+假手術(shù)組、MA依賴+蒸餾水組中表達(dá)均升高,而在MA依賴+GDNF低劑量干預(yù)組和MA依賴+GDNF高劑量干預(yù)組中表達(dá)降低；DAT及其mRNA在單純MA依賴組MA依賴+假手術(shù)組、MA依賴+蒸餾水組中表達(dá)均降低,而MA依賴+GDNF低劑量干預(yù)組和MA依賴+GDNF高劑量干預(yù)組中表達(dá)明顯回升。結(jié)論：1.采用多次腹腔注射甲基苯丙胺,結(jié)合條件性位置偏愛(ài)實(shí)驗(yàn)的方法成功建立甲基苯丙胺依賴大鼠模型。2.GDNF可改變甲基苯丙胺依賴大鼠伏隔核DRD2、DAT及其mRNA的表達(dá),提示GDNF對(duì)甲基苯丙胺所致毒性作用有治療保護(hù)作用。GDNF在0.5μg/μl和1.0μg/μl時(shí)均能有效改變甲基苯丙胺所致的DRD2及DAT及其mRNA的表達(dá)變化,其中在0.5μg/μl時(shí)的治療干預(yù)效果較好。
[Abstract]:Aim: to establish a rat model of MA-dependent methamphetamine, and to observe the changes of dopamine D2 receptor (DRD2) and dopamine transporter (DATs) in nucleus accumbens and intracerebroventricular injection of glial cell-derived nutrition factor (GDNF) in MA-dependent rats.To investigate the effect of exogenous GDNF intervention on the metabolism of nucleus accumbens in methamphetamine-dependent rats.Methods 160 Sprague-Dawley rats were randomly divided into three groups: one week, four weeks and eight weeks dependent groups.The three experimental groups were divided into five subgroups: the MA dependent group, the MA dependent sham operation group, the MA dependent distilled water group, the MA dependent GDNF low dose intervention group, and the MA dependent GDNF high dose intervention group.The changes of DRD2DAT protein and its mRNA in nucleus accumbens were detected by immunohistochemistry, in situ hybridization, Western blot and real-time quantitative PCR.The result is 1: 1.Compared with the control group, there were significant differences among the three simple methamphetamine dependent groups in conditioned place preference (CPP) experiments, and the methamphetamine dependent rat model was established successfully.Compared with the control group, the expression of DRD2DAT in the nucleus accumbens and its mRNA were all increased in the MA dependent sham-operated group and the distilled water group.In MA dependent GDNF low dose intervention group and MA dependent GDNF high dose intervention group, the expression of mRNA was decreased in MA dependent sham operation group and distilled water group.However, the expression of MA-dependent low-dose GDNF and MA-dependent high-dose GDNF increased significantly.Conclusion 1.The rat model of methamphetamine dependent rats was successfully established by intraperitoneal injection of methamphetamine. 2. GDNF could change the expression of DRD2DAT and its mRNA in the nucleus accumbens of methamphetamine dependent rats.The results suggest that GDNF can effectively change the expression of DRD2, DAT and mRNA at 0.5 渭 g / 渭 l and 1.0 渭 g / 渭 l, especially at 0.5 渭 g / 渭 l.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：D919.1

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