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研究生: 柯孟昌
Meng-Chang Ko
論文名稱: 周邊發炎反應誘發MPTP對小白鼠神經毒害之加成作用
Systemic Inflammation Induce Synergistic Neurotoxicity of the MPTP in the Mice
指導教授: 黃基礎
Hwang, Ji-Chuu
呂國棟
Lu, Kwok-Tung
學位類別: 碩士
Master
系所名稱: 生命科學系
Department of Life Science
論文出版年: 2005
畢業學年度: 93
語文別: 中文
論文頁數: 68
中文關鍵詞: 巴金森氏症周邊發炎反應氧化壓力白藜蘆醇
論文種類: 學術論文
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  • 壹、中文摘要
    巴金森氏症是常見的漸進性神經退化性疾病,最近的相關研究認為巴金森氏症成因可能是多項致病因素綜合的結果,包含暴露於環境中有害毒物,以及中樞神經發炎反應皆可能增加致病的風險。在離體實驗中,以內毒素(lipopolysaccharide ; LPS)預先誘發的發炎反應會增加神經毒素rotenone的毒害效果。在本實驗中,同時給予內毒素與神經毒素1-甲基4-酚基-1,2,3,6-四氫嘌呤(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine;MPTP)處理的老鼠在運動功能測試儀(rota-rod)行為表現能力有顯著的下降,而在抓力測試(grasp strengthen)的結果也發現抓力有顯著的增強,組織切片染色亦發現黑質緻密區(pars compacta of substantia nigra)神經細胞數降低、多巴胺神經細胞減少的現象。顯示發炎反應是會加重病情的進展。實驗中發現,若合併投予抗氧化藥物白藜蘆醇(resveratrol),則發炎所引起的MPTP毒性加成效果大為減緩。利用微透析技術(microdialysis)與高效液相層析法(high performance liquid chromatography),亦發現resveratrol可減緩小白鼠黑質部位的氧化壓力。顯示發炎反應所引發的自由基增加,對於MPTP在黑質紋狀體路徑毒害效果具有重要的影響性,而resveratrol抗氧化的功能可減緩自由基對神經細胞的毒害,達到保護效果。

    貳、英文摘要
    Parkinson’s disease (PD) is a common progressive neurodegenerative disease. Recent results suggest that PD may represent the final outcome of complicated interactions, including exposure to environmental toxins and the occurrence of inflammation in the brain. In vitro test , the combination of rotenone with lipopolysaccharide (LPS) could enhance the neurotoxic effect of rotenone. Our present results showed that mice receiving a co-treatment of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) with LPS reduced the rota-rod activities but strengthened the grasp ability and reduced the survival ratio of dopaminergic neuron in the pars compacta of substantia nigra (SNpc). Furthermore, pretreatment of resveratrol, an antioxidation drug, could reduce the neurotoxic effect of LPS. Using microdialysis and high performance liquid chromatography, we demonstrated that oxidative stress in SNpc was reduced by resveratrol. These results suggest that systemic inflammation may play an important role in selective destruction of nigrostriatal dopaminergic neurons by MPTP and resveratrol could decrease oxidative stress and protect dopaminergic neurons.

    目錄 壹、 中文摘要 (Abstract in Chinese)---------------------------------- 3 貳、 英文摘要 (Abstract in English)---------------------------------- 5 參、 緒論 (Introduction) 一、研究背景 (Study Background)-------------------------------------9 二、問題與假設 (Question and hypothesis)-----------------------17 三、研究目的 (Study purposes)---------------------------------------17 肆、 研究材料與方法 (Materials and Methods) 一、 實驗動物 (Animals)--------------------------------------------- 20 二、 實驗藥品 (Drugs)------------------------------------------------20 三、 動物分組 (Animals grouping) ------------------------------- 21 四、 行為測試 (Behavioral experiments)-------------------------22 五、 組織冷凍切片 (Tissue frozen section)----------------------23 六、 組織學鑑定 (Histochemistry)----------------------------------24 七、 神經細胞數目計算 (Neural cell number counting)-------25 八、 氫氧自由基偵測 (Hydroxyl radicals detection)-----------25 九、 統計方法 (Statistical analysis)-------------------------------27 伍、 結果 (Results)----------------------------------------------------------28 陸、 討論 (Discussion)-----------------------------------------------------39 柒、 參考文獻 (References)----------------------------------------------46 捌、 附圖 (Figures)---------------------------------------------------------55

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