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研究生:朱家慧
研究生(外文):Chia-Hui Chu
論文名稱:慢性低劑量Deprenyl處理減輕高劑量甲基安非他命對大白鼠的神經毒性:行為及腦區GFAP與TH免疫組織化學染色的研究
論文名稱(外文):Chronic Low Dose Deprenyl Attenuate The High Dose Methamphetamine-Induced Neurotoxicity in Rat : Studies in Behavior and Brain Regional GFAP and TH Immunohistochemical Expression.
指導教授:黃銀河黃銀河引用關係
指導教授(外文):Yn-Ho Huang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:解剖暨細胞生物學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2006
畢業學年度:94
語文別:中文
論文頁數:54
中文關鍵詞:甲基安非它命行為改變膠質原纖維酸性蛋白酥胺酸羥化酵素
外文關鍵詞:methamphetaminedeprenylbehaviorGFAPTH
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甲基安非他命是精神亢奮劑, 也是一種全球性濫用的毒品。高劑量甲基安非他命會造成嚴重的腦功能受損, 引起腦部多巴胺過量釋放, 導致過氧化物的大量堆積,使得神經細胞凋亡。Deprenyl 是一種不可逆的單胺氧化酶抑制劑,多項研究指出其低劑量Deprenyl可清除自由基、降低氧化性傷害,提供神經保護的作用,臨床上也用作治療帕金森氏症的輔助用藥。因此,本實驗擬以慢性低劑量Deprenyl處理(0.25 mg/kg, IP,每天一次)來檢驗其對高劑量之甲基安非他命(5 mg/kg, IP, 每二小時一次, 共四次)引發之神經細胞受損的治療效果。利用行為測試及TH 與GFAP免疫組織化學染色的方法來探討Deprenyl是否可以減緩高劑量甲基安非他命所引起的神經毒性。
實驗結果顯示:(1)在行為方面,和對照組相較之下,第一天甲基安非他命處理組的大白鼠,有活動力及刻板行為增加的表現;認知指數有顯著降低;在免疫組織染色方面:多巴胺系統的核區(包含內側前額腦區(MPC), 尾狀殻核(CPU), 下視丘弓狀核(ARC), 黑質緻密區(SNC) , 中央灰質部(CG)及 腹側被蓋區(VTA)等區),TH的表現量明顯下降及GFAP表現量明顯上升,顯示甲基安非他命所引起的毒性;(2) 慢性Deprenyl處理後,顯著改善了甲基安非他命引起的認知指數降低;在免疫組織染色方面也有明顯減緩甲基安非他命所引起的病兆。由此初步結果可知,慢性處理低劑量Deprenyl可減緩甲基安非他命所引起的神經毒性, 推測過氧化自由基的形成在甲基安非他命的神經毒性中扮演重要角色。
Methamphetamine (MAP) is an illicit drug of psychostimulant and has been abused worldwide. High dose MAP can cause severe neurotoxic effects involving the overloading of dopamine, oxidative free radicals, and apoptosis. Deprenyl, an irreversible inhibitor of monoamine oxidase B, has been used clinically to treat adjunctively the Parkinson’s disease and Alzheimer’s disease because of its neuroprotective effect. This effect can only accomplished at its low anti-apoptotic dose. However, the neuroprotective mechanism of deprenyl is still unclear. In this study, we used low dose chronic deprenyl ( 0.25 mg/kg/day, IP )to study if deprenyl can reduce the high dose MAP ( 5mg/kg,IP, given 4 times consecutively in a day at 2 hr interval ) neurotoxicity in rats. The behavior (locomotion, recognition index) rating and brain regional GFAP and TH immunohistochemical expression were used to evaluate the results. The results showed that MAP reduce significantly the recognition index of objects in rat and the deprenyl treat recover the deficit. MAP reduced significantly the TH expression in regions of dopamine circuits, such as MPC, CPU, ARC, SNC, CG, and VTA, while deprenyl recovered it. In addition, Map increased significantly the GFAP expression in regions of dopamine circuits aforementioned, while deprenyl recovered it. In conclusion, we suggest that low dose chronic deprenyl can effectively attenuate the deficits caused by the MAP-induced neurotoxicity.
英文摘要
中文摘要
名詞縮寫
序言
一、 中神經興奮劑--甲基安非他命………………………1
二、 Deprenyl………………………………………………4
三、 膠質原纖維酸性蛋白---GFAP……………………….6
四、 酥胺酸羥化酵素---TH………………………………..7
研究目的……………………………………………………..8
材料與方法
一、 實驗動物…………………………………………….9
二、 實驗藥品…………………………………………….9
三、 實驗設計及流程…………………………………….9
四、 資料分析……………………………………………13
結果
一、 前處理行為測試結果………………………………16
二、 認知記憶測試結果…………………………………17
三、 免疫組織化學染色結果……………………………18
討論…………………………………………………………..23
圖表……………………………………………………………………29
參考文獻………………………………………………………………49
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