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研究生:張明祥
研究生(外文):Ming-Hsiang Chang
論文名稱:山藥薯蓣皂素添加於老化大鼠飲食中對其空間學習與記憶能力之影響
論文名稱(外文):Effects of diosgenin on spatial learning and memory in aging rat
指導教授:金亭佑
指導教授(外文):Ting-Yu Chin
學位類別:碩士
校院名稱:中原大學
系所名稱:生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2015
畢業學年度:104
語文別:中文
論文頁數:59
中文關鍵詞:山藥薯蕷皂素神經退化性疾病老化神經保護
外文關鍵詞:DiosgeninNeurodegenerationAgingNeuroprotection
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老化是造成神經退化性疾病增加的主因之一,如何改善老化所造成認知行為能力下降是一個重要議題。山藥薯蕷皂素 (Diosgenin) 是一種類固醇皂苷元,存在於山藥中。文獻指出山藥薯蕷皂素對中樞神經系統具有保護作用。我們餵食19月齡SD (Sprague-Dawley) 大鼠8週含或不含 0.1 wt% 山藥薯蕷皂素飼料,觀察其是否對19月齡大鼠具有神經保護作用。在莫利斯水津迷宮行為測試數據中,實驗組與控制組相比,山藥薯蕷皂素提高了19月齡大鼠的空間記憶與工作記憶能力。在 Y 字迷宮行為測試中,山藥薯蕷皂素組表現比控制組更好的空間辨識記憶。在海馬迴中,山藥薯蕷皂素降低了 IL-1β mRNA 的表現量,但不影響 TNF-α、iNOS、BDNF 的表現。在西方墨點法分析中,山藥薯蕷皂素提高了synaptophysin和PSD95 (postsynaptic density protein 95) 在海馬迴中的含量,並顯著降低磷酸化 tau 在海馬迴中的表現。在海馬迴切片染色的結果中,顯示山藥薯蕷皂素無法促進神經元增生,但顯著的降低微膠細胞的活化。這些結果指出山藥薯蕷皂素具有改善老化造成的認知能力衰退,可能是經由降低微膠細胞活化作用和避免突觸功能喪失。

Aging is an important risk factor for the pathogenesis of neurodegenerative diseases. Therefore, the treatment and prevention of neurodegenerative diseases are one of the most important public health problems. Diosgenin (3β-hydroxy-5-spirostene), a naturally occurring steroid saponin found abundantly in yams. Previous reports have been indicated that diosgenin possess the function of neuroprotection. Herein, we want to investigate the neuroprotective effects of diosgenin on aging rats (19 months old). We compared the behavior of aging rats fed diets with or without 0.1 wt% diosgenin for 8 weeks. The results indicated that spatial learning and memory ability of aging rats fed with diet containing diosgenin is better than control group in Morris water maze test. Compared to control, diet containing diosgenin could induced aging rats preferred to explore a new arm compared with conteol group in Y-shaped maze test. In addition, diosgenin-induced down-regulation of the expression of IL-1β, whereas the epression of TNF-α and iNOS was not changed in the hippocampus of aging rats by RT-QPCR. Additionally, diosgenin-treatment induced significantly reduction of phosphorylation of tau and increased the expression of the presynaptic proteins synaptophysin and postsynaptic PSD95 in the hippocampus of aging rats by Western blot analysis. Furthermore, by evaluating the immunohistochemical results of iba1 staining showed that diosgenin attenuated microgial activation; however, Ki67 staining indicated that the cell proliferation was not affected. These results suggest that diosgenin ameliorate age dependent cognitive deficits which may be partly mediated via suppression of activated microgial and preventing synaptic dysfunction.

目錄
摘要-----------------------------------------------------------I
Abstract------------------------------------------------------II
致謝---------------------------------------------------------IV
目錄----------------------------------------------------------V
圖目錄------------------------------------------------------VIII
附圖目錄-----------------------------------------------------IX
縮寫表--------------------------------------------------------X
第一章 前言---------------------------------------------------1
第二章 文獻回顧-----------------------------------------------2
第一節 老化對神經退化性疾病之影響-------------------------2
第二節 雌激素對腦部之影響----------------------------------2
一、雌激素-----------------------------------------------2
二、雌激素對突觸可塑性之影響----------------------------2
三、雌激素對海馬迴神經新生之影響------------------------4
第三節 山藥薯蕷皂素----------------------------------------5
第三章 研究動機-----------------------------------------------7
第四章 實驗方法與材料-----------------------------------------8
第一節 研究材料 --------------------------------------------8
一、藥品試劑---------------------------------------------8
二、實驗器材--------------------------------------------10
第二節 大鼠飼育--------------------------------------------12
第三節 飼料配置--------------------------------------------12
第四節 莫利斯水津迷宮行為測試 -----------------------------13
第五節 Y字迷宮行為測試------------------------------------15
第六節 冷凍組織切片免疫染色-------------------------------16
第七節 即時定量反轉錄聚合酶連鎖反應 (qRT-PCR)------------17
第八節 西方墨點法 (Western blot)---------------------------18
第九節 統計分析--------------------------------------------19
第五章 結果--------------------------------------------------20
第一節 山藥薯蕷皂素對老化大鼠空間記憶與學習能力之影響---20
第二節 山藥薯蕷皂素對老化大鼠空間辨識記憶能力之影響------21
第三節 山藥薯蕷皂素對老化大鼠腦中發炎因子表現之影響------22
第四節 山藥薯蕷皂素對老化大鼠腦中神經滋養因子表現之影響--22
第五節 山藥薯蕷皂素對老化大鼠腦中突觸蛋白表現之影響------23
第六節 山藥薯蕷皂素對老化大鼠腦中磷酸化 tau 表現之影響----23
第六章 討論---------------------------------------------------24
第一節 山藥薯蕷皂素改善老化大鼠之空間記憶與學習能力------24
第二節 山藥薯蕷皂素降低老化大鼠之磷酸化 tau 的表現--------25
第七章 結論---------------------------------------------------27
參考文獻------------------------------------------------------28
圖表----------------------------------------------------------34
附錄----------------------------------------------------------44

圖目錄
圖一、實驗架構流程圖-----------------------------------------34
圖二、莫利斯水津迷宮行為測試---------------------------------35
圖三、空間記憶測試-------------------------------------------36
圖四、Y字迷宮行為測試----------------------------------------37
圖五、大腦皮層和海馬迴中發炎因子 mRNA 表現量---------------38
圖六、大腦皮層和海馬迴中神經滋養因子表現量------------------39
圖七、海馬迴中突觸蛋白表現量---------------------------------40
圖八、海馬迴中磷酸化tau表現量--------------------------------41
圖九、海馬迴中 ki67-positive cell 數量-------------------------42
圖十、海馬迴中 iba1-positive cell 數量-------------------------43

附圖目錄
附圖一、象限設計示意圖---------------------------------------44
附圖二、水迷宮試驗流程圖-------------------------------------45
附圖三、Y字迷宮設計示意圖------------------------------------46
附圖四、diosgenin 結構----------------------------------------47
附圖五、雌激素 (E1-E3) 化學結構圖-----------------------------48
附圖六、莫利斯水津迷宮測試-----------------------------------49


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