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研究生: 張芸瑄
Zhang, Yun-Xuan
論文名稱: 探討δ-生育三烯醇對甲基乙二醛誘導小鼠腦神經損傷之保護效果
Study on the protective effect of δ-tocotrienol on methylglyoxal-induced cranial nerve injury in mice
指導教授: 陳與國
Chen, Yu-Kuo
學位類別: 碩士
Master
系所名稱: 農學院 - 食品科學系所
Department of Food Science
畢業學年度: 107
語文別: 中文
論文頁數: 77
中文關鍵詞: 甲基乙二醛神經退化性疾病阿茲海默症生育三烯醇
外文關鍵詞: methylglyoxal, neurodegenerative disease, Alzheimer’s disease, tocotrienol
DOI URL: http://doi.org/10.6346/NPUST201900285
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  • 甲基乙二醛 (Methylglyoxal, MG),為糖基化終產物 (Advanced glycation end product, AGEs) 的前驅物,會在中樞神經系統中引起神經元功能障礙,其累積與多種疾病相關,例如:糖尿病及神經退化性疾病。阿茲海默症 (Alzheimer’s disease, AD) 為最常見的神經退化性疾病,主要症狀為影響患者的記憶、思維、甚至是維持日常生活的能力,而老年斑塊積累以及神經原纖維纏結為典型的病理特徵。維生素E為生育三烯醇 (Tocotrienol, T3) 及生育醇 (Tocopherol, T) 之統稱。具有抗氧化、抗老化、抗炎及神經保護等多種生理活性。文獻指出,生育三烯醇之抗氧化及抗炎等生理活性優於生育醇。本實驗選用δ-生育三烯醇作為實驗樣品,探討其在小鼠腦內對於甲基乙二醛所誘導神經損傷之保護效果,評估δ-生育三烯醇是否具有保護腦神經之潛力。實驗結果顯示,餵食δ-T3對小鼠之體重及攝食量並無顯著性影響。水迷宮試驗結果顯示,餵食δ-T3後,與負控組相比,小鼠之空間記憶學習能力有回復之趨勢。而以western blot結果顯示,餵食δ-T3後,與負控組相比,PI3K、p-Akt、p-GSK-3β及BDNF之蛋白表現量提升,且p-Tau、Aβ1-42及cleaved-caspase 3之蛋白表現量下降。總結以上結果,δ-T3具有保護MG誘導小鼠腦神經損傷之功效。

    Methylglyoxal (MG), a precursor of glycation end products (advanced glycation end product, AGEs), induces various stress responses in the central nervous system and causes neuronal dysfunction, and is associated with a variety of diseases, such as diabetes and neurodegenerative diseases. Alzheimer's disease (AD) is the most common neurodegenerative disease. The main symptoms are affecting the patient's memory, thinking, and even the ability to maintain daily life. Age-related plaque accumulation and neurofibrillary tangles are important typical features of Alzheimer’s disease. Vitamin E is a collective name for tocotrienol (T3) and tocopherol (T). It has many physiological activities such as anti-oxidation, anti-aging, anti-inflammatory and neuroprotection. The literature indicates that the physiological activity of T3 is better than tocopherol. In this experiment, δ-T3 was selected as an experimental sample to investigate its protective effect on nerve damage induced by methylglyoxal in mice, and to evaluate whether δ-T3 has the potential for protection of cranial nerve. The experimental results showed that the feeding of δ-tocotrienol had no significant effect on the body weight and food intake of the mice. The water maze test results showed that after feeding δ-tocotrienol, the spatial memory learning ability of mice was reverted compared with the negative control group. Western blot analysis showed that after feeding δ-T3, the protein expression of PI3K, p-Akt, p-GSK-3β and BDNF was increased compared with the negative control group, and the protein expression of p-Tau, Aβ1-42 and cleaved-caspase3 was decreased. Summarize the above results, δ-T3 has the protective effects on brain damage induced by MG in mice.

    摘 要 I
    Abstract II
    目 錄 VI
    圖目錄 VIII
    表目錄 IX
    壹、 前言 1
    貳、 文獻回顧 2
    一、 維生素E 2
    (一) 生育三烯醇 2
    (二) 生育三烯醇之吸收代謝 2
    (三) 生育三烯醇之生理活性 3
    (四) 生育三烯醇於神經保護方面之研究 4
    二、 神經退化性疾病 4
    (一) 阿茲海默症 (Alzheimer's disease, AD) 4
    (二) 阿茲海默症發展進程 5
    (三) 阿茲海默症相關蛋白 5
    (四) 阿茲海默症之治療與預防 7
    三、 甲基乙二醛 7
    (一) 甲基乙二醛概述 7
    (二) 甲基乙二醛的合成 7
    (三) 甲基乙二醛涉及之病理條件 8
    (四) 甲基乙二醛於神經病理學上之影響 8
    參、 材料與方法 20
    一、 實驗架構 20
    二、 實驗材料與儀器 21
    (一) 實驗樣品 21
    (二) 實驗藥品與溶劑 21
    (三) 實驗儀器 24
    (四) 實驗動物、飼料用材料及動物實驗用器材 27
    三、 實驗方法 28
    (一) 動物飼養 28
    (二) 行為測試 28
    (三) 實驗動物採血及犧牲 29
    (四) 實驗動物血液分析 30
    (五) 西方轉漬法 (Western blot) 30
    (六) 統計分析 36
    肆、 結果與討論 37
    一、 δ-T3對於實驗動物生長狀況及攝食量之變化 37
    二、 δ-T3對於實驗動物空間記憶學習能力之影響 37
    三、 小鼠血漿中葡萄糖 (Glu) 濃度之分析 38
    四、 小鼠血漿中丙胺酸轉胺酶 (ALT) 濃度之分析 38
    五、 小鼠腦組織切片分析 39
    六、 δ-T3對小鼠海馬迴中神經調控相關蛋白之影響 39
    伍、 結論 43
    陸、 實驗圖表 44
    柒、 參考文獻 62
    捌、 作者簡介 76

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