- 學位論文
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
Effects of diosgenin on spatial learning and memory in aging rat
摘要
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。
並列摘要
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.