臺灣博碩士論文加值系統

　　Nifedipine是一種dihydropyridine類的藥劑，可以抑制L型鈣離子通道(L-type calcium channel)。在過去的研究中指出，對雄性大鼠腹腔注射nifedipine藥劑並無顯著的影響雄性大鼠被動逃避反應測試(passive avoidance)記憶反應，但如果使用埋管注射法直接對雌性Wistar大鼠兩側海馬迴做直接注射nifedipine，則有輕微增強雌性大鼠對被動逃避反應測試的表現能力。相對於記憶測試結果，有許多的電生理研究結果指出nifedipine不會影響大鼠海馬迴LTP ( long-term potentiation )的維持能力。本實驗嘗試以記憶測試時經常使用的C57BL6J品系小鼠為實驗動物，並嘗試用埋管注射法直接對小鼠兩側海馬迴注射nifedipine藥劑，並使用被動逃避反應測試與Morris水迷宮來評估nifedipine 敏感性 L型鈣離子通道對C57BL6J品系小鼠記憶形成的影響。結果顯示，無論低劑量(0.1μM)或高劑量(100μM)的 nifedipine溶液0.2μl注入小鼠兩側海馬迴，對雄性小鼠的被動逃避反應與水迷宮表現能力並無顯著的影響；而使用低劑量(0.1μM)的nifedipine溶液 0.2μl注入海馬迴，則可顯著的增強雌性小鼠的被動逃避反應表現能力，但是對雌性小鼠的水迷宮表現情形則無顯著影響。由被動逃避測試實驗結果顯示，低劑量nifedipine藥劑對不同性別小鼠作用效果並不一致，可能是nifedipine對雌雄小鼠海馬迴的L型鈣離子通道作用效果不同，或是雌雄小鼠腦部基本特性不同所導致，但是影響機制仍然不清楚；低劑量的nifedipine藥劑注射會增強雌性小鼠被動逃避測試反應能力，但是並不會影響其水迷宮空間記憶能力，也顯示在不同的記憶模式下，L型鈣離子通道對於記憶的形成有不同的效果。

　　Nifedipine is a dihydropyridine agent and a L-type calcium channel antagonist. It had been demonstrated by some investigators that intraperital injection of nifedipine could not decrease ability of passive avoidance in male rats, while the bilateral hippocampus infusion could slightly increase in female Wistar rats. In contrast, many electrophysiological researches revealed that nifedipine had no influnce on the maintenance of LTP (long-term potentiation) in hippocampus. In this experiment, we tried to implant cannel and infuse nifedipine into bilateral hippocampus of C57BL6J mice, a common animal model in many memory experiment, and to estimate the effects of nifedipine sensitive L-type calcium channel on memory of C57BL6J mice by using passive avoidance test (PAT) and Morris water maze (MWM). Our results shown that neither a low dose (0.1μM) nor a high dose (100μM) of nifedipine in 0.2μl did not change the ability of PAT and MWM in male C57BL6J mice. However, a low dose (0.1μM) of nifedipine caused a significant increase in the ability of PAT without an influence on the MWM in female C57BL6J mice with the same treatment. These results suggest that in a low dose nifedipine the responses of PAT in both sexes of mice are different, and it maybe due to a different effects of nifedipine upon L-type calcium channels or maybe due to a sexual difference in brain characters of C57BL6J mice. In addition, a low dose of nifedipine shows an enhance on the ability of PAT but not on MWM in female C57BL6J mice indicating the existence of a different effect of L-type calcium channel on memory experiment.

中文摘要 Ⅰ
英文摘要 Ⅱ
致謝 Ⅲ
目錄 Ⅳ
表目錄 Ⅵ
圖目錄 Ⅷ

壹、前言 1

貳、材料與方法 4
　　一、實驗動物 4
　　二、藥物 4
　　三、埋管規格 4
　　四、動物手術 5
　　五、藥物注射 5
　　六、動物模式測驗 6
　　　　1.被動逃避反應測試 6
　　　　2.運動能力測試 7
　　　　3.水迷宮測試 7
　　七、染色定位與切片 8
　　八、統計分析 8

參、結果 16
　　一、海馬迴注射結果 16
　　二、運動稜力測試 18
　　三、被動逃避反應測試 22
　　四、水迷宮測試 27

肆、討論 42

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