指導教授：潘子明臺灣大學：生化科技學系郭睿Kuo, JuiJuiKuo2014-11-262018-07-062014-11-262018-07-062014http://ntur.lib.ntu.edu.tw//handle/246246/261613腦中風再灌流 (cerebral stroke reperfusion) 之傷害過程包含氧化壓力產生、引發細胞凋亡等，本研究使用八週齡大之雄性 Sprague-Dawley 大鼠，以雙側總頸動脈阻斷再灌流之手術引發腦中風，造成學習記憶能力之衰退，而紅麴米萃取物及二次代謝物 lovastatin 能有效改善大鼠記憶功能損傷。腦中風使大鼠腦中之 glial fibrillary acidic protein (GFAP) 表現量增加，而紅麴米萃取物及二次代謝物 lovastatin 能降低其表現，另外亦能降低腦中氧化壓力及凋亡現象，對照劑 melatonin 也加入評估，而效果不顯著。本研究結果顯示紅麴能增加抗氧化酵素活性並減少malondialdehyde (MDA) 之產生，抑制凋亡現象及降低 GFAP 表現，而最後改變腦中風造成之記憶學習能力損傷，且效果較 melatonin佳。證明紅麴米萃取物及二次代謝物 lovastatin 能夠延緩並改善腦中風之病理狀況。Oxidative stress and apoptosis induced from cerebral stroke-reperfusion are involved in the cerebral stroke and reperfusion processes of impairment. In this research, every male Sprague-Dawley rats accept bilateral common carotid artery occlusion-reperfusion operation to induce memory and learning ability impairment of stroke. We examined the beneficial effects of the extract and secondary metabolite of red mold rice (RMR) in this model. The extract and secondary metabolite of RMR could improve cognitive impairment in behavior tests. We also found that extract and secondary metabolite of RMR reduce the expression of red mold rice glial fibrillary acidic protein (GFAP) which is elevated by stroke. Furthermore, the extract and secondary metabolite of RMR could reduce oxidative stress and apoptosis in rat’s brain. Effects of melatonin, as a contrast agent, was also examined in this research and show no significant improvement. This research shows that by suppressing lipid peroxidation and activating antioxidant enzyme, the extract and secondary metabolite of RMR could reduce oxidative stress and apoptosis and then ameliorates stroke pathology finally. Thus, protects rats against the impairment of memory and learning ability induced by stroke. In addition, these advantageous effects of the extract and secondary metabolite of RMR on stroke are even better than melatonin. This research proves that the extract and secondary metabolite of RMR could protect the brain from stroke and have multifunctional property in stroke treatment.目 錄 縮寫表…………………………………………………………………………………………………………………………. i 中文摘要…………………………………………………………………………………………………………………….. iii 英文摘要……………………………………………………………………………………………………………………… iv 目錄…………………………………………………………………………………………………………………………….. v 圖目錄…………………………………………………………………………………………………………………………. vii 第壹章 文獻回顧…………………………………………………………………….….……………………………… 1 一、腦中風…………………………………………………………………………………………………………………. 1 (一) 腦中風之簡介……………………………………………………………………………………………………. 1 (二) 腦中風之病理機制……………………………………………………………………………………………. 3 (三) 腦中風之動物模式……………………………………………………………………………………………. 6 (四) 現行腦中風之治療方式…………………………………………………….……………………………… 9 二、紅麴……………………………………………………………………………………………………………………… 11 (一) 紅麴菌種之特性……………………………………………………………………………………………….. 11 (二) 紅麴之二次代謝物及功效…………………………………………………………………………………. 12 (三) 紅麴與腦中風……………………………………………………………………………………………………. 15 第二章 研究動機與大綱…………………………………………………………………….……………………… 17 第三章 材料與方法……………………………………………………………………………………………………. 19 ㄧ、實驗材料……………………………………………………………………………………………………………… 19 (一) 儀器…………………………………………………………………………………………………………………… 19 (二) 藥品…………………………………………………………………………………………………………………… 19 二、實驗方法……………………………………………………………………………………………………………… 20 (一) 動物實驗…………………………………………………………………………………………………………... 20 (二) 生化分析…………………………………………………………………………………………………………… 30 (三) 統計分析方法……………………………………………………………………………………………………. 32 第四章 結果與討論……………………………………………………………………………………………………. 33 ㄧ、實驗動物之飼養與生長狀況………………………………………………………………………………. 33 二、以雙側總頸動脈阻斷 30 分鐘再灌流手術誘導腦中風……………………………………. 33 三、紅麴米萃取物對腦中風大鼠學習記憶能力之改善……………………………………………. 33 四、紅麴米萃取物對腦中風大鼠病理狀況之改善效果………………………………………….. 42 五、綜合討論……………………………………………………………………………………………………………. 50 第五章 總結……………………………………………………………………………………………………………….. 53 第六章 參考文獻………………………………………………………………………………………………………… 542972650 bytesapplication/pdf論文公開時間：2017/08/25論文使用權限：同意有償授權(權利金給回饋本人)中風紅麴再灌流水迷宮被動迴避thesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/261613/1/ntu-103-R00b22034-1.pdf