指導教授：潘子明臺灣大學：生化科技學系楊承翰Yang, Cheng-HanCheng-HanYang2014-11-262018-07-062014-11-262018-07-062014http://ntur.lib.ntu.edu.tw//handle/246246/261601In the recent research, it has been discovered that red mold rice has the potential to ameliorate the symptom of Alzheimer’s disease (AD), by the functional factor such as monacolin K, γ-aminobutyric acid (GABA), dimerumic acid, ankaflavin and monascin. Using dioscorea as substrate for Monascus purpureus fermentation, it can produce higher amount of functional ingredients, ankaflvin and monascin. In this study, we investigate the effect of red mold dioscorea (RMD) to ameliorate Alzheimer’s disease pathophysiology. Using 4 month-old Alzheimer’s disease transgenic mice J20 feeding with RMD for two months, we found that J20 mice fed with RMD have better learning and memory ability then the control group in behavior test such as passive avoidance and Morris water maze. Analyzing the symptoms related to AD, we found that in the brain of J20 mice fed with RMD, there’s a significant decrease in the amount of Aβ1-40, 1-42 and enzyme activity of acetylcholinesterase. After confirming the effect of RMD in AD, we use positive control, rosiglitazone group as reference to investigate the mechanism of RMD to ameliorate AD. In decreasing p-tau level, activating the CD36 marker gene expression which related to microglia clearing Aβ, decreasing gene expression of γ-secretase, we found that RMD has the same effect as rosiglitazone, a PPARγ agonist. According to the previous research that pigments in RMD, monascin and ankaflavin, have the characteristic of PPARγ agonist combined with our results, we assumed that one of the mechanism of RMD to ameliorate AD may through monascin and ankaflavin, as PPAR γagonist rosiglitazone, activate PPARγ to effect it.目 錄 謝誌..........................................................I 縮寫表........................................................II 中文摘要......................................................IV 英文摘要.......................................................V 目錄..........................................................VI 表目錄......................................................VIII 圖目錄.........................................................IX 第壹章 文獻回顧..................................................1 ㄧ、阿茲海默症之文獻回顧...........................................1 (一) 阿茲海默症與失智症..........................................1 (二) 阿茲海默症形成機制..........................................2 (三) 阿茲海默症之治療藥物.........................................6 二、PPAR γ促效劑與阿茲海默症......................................10 (一) 調控類澱粉蛋白代謝..........................................11 (二) 調控能量代謝...............................................11 (三) 降低發炎反應...............................................13 (四) 調節血脂...................................................13 三、實驗餵食樣品..................................................14 (ㄧ) 紅麴山藥...................................................14 (二) 梵蒂亞.....................................................18 四、阿茲海默症基因轉殖鼠............................................19 第貳章 研究動機與目的..............................................23 第參章 材料與方法..................................................25 ㄧ、實驗材料......................................................25 二、實驗方法......................................................27 第肆章 結果與討論..................................................38 ㄧ、基因轉殖鼠基因型態鑑定...........................................38 二、餵食紅麴山藥、rosiglitazone八周後對J20小鼠記憶學習能力之影響.........38 三、餵食紅麴山藥、rosiglitazone八周後對J20小鼠體重之影響...............45 四、安全性試驗分析.................................................45 五、餵食紅麴山藥、rosiglitazone八周後對J20小鼠腦中類澱粉蛋白之影響.......48 六、餵食紅麴山藥、rosiglitazone八周後對J20小鼠腦中乙醯膽鹼酯酶活性之影響..54 七、餵食紅麴山藥、rosiglitazone八周後對J20小鼠腦中基因表現量之影響.57 八、餵食紅麴山藥、rosiglitazone八周後對J20小鼠腦中P-tau蛋白之影響.60 九、餵食紅麴山藥、rosiglitazone八周後對J20小鼠腦中的抗氧化能力之影響60 十、餵食紅麴山藥、rosiglitazone八周後對J20小鼠腦中細胞激素TNF-α 之影響69 第伍章 結論.......................................................74 第陸章 參考文獻....................................................764641366 bytesapplication/pdf論文使用權限：不同意授權阿茲海默症基因轉殖鼠J20紅麴山藥rosiglitazonemonascinankaflavinPPARγ 促效劑。thesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/261601/1/ntu-103-R01b22029-1.pdf