斑馬魚是一種脊椎動物，它的胚胎透明— 方便觀察器官形成、產卵率高— 平均一週有200 ~ 300顆的產量、飼養容易、成本低，且斑馬魚在型態學上的模式有完整的資訊，而斑馬魚的基因組分析也已接近完成。在發育生物學及遺傳分子學中，斑馬魚佔有很大的優勢。而這些優勢，可以用來當做大規模篩選食品與藥物中毒性與機制的工具。本篇論文即是利用斑馬魚當作模式物種，並設計一個篩選食品與藥物的平台。斑馬魚胚胎對於苯甲酸鈉、咖啡因、順鉑、釕金屬在運動能力或腎臟毒害情形中，有不同程度的耐受情形。結果顯示，在運動能力上，暴露10 ppm 以上的苯甲酸鈉會降低斑馬魚游動能力，當暴露2000 ppm 的苯甲酸鈉時斑馬魚幾乎沒有游動能力。在腎毒性的研究上，暴露500 ppm 以上的苯甲酸鈉，暴露75 ppm 以上的咖啡因，暴露20 ppm 以上的順鉑和暴露75 ppm 以上的釕金屬化合物，對於斑馬魚腎臟仍是有產生毒害情形。綜合以上結果，本論文所設計的篩選平台，可以降低成本及有效率的篩選食品與藥物，是否具有毒性，尤其是腎臟方面的研究。

Zebrafish (Danio rerio) is a good model for large-scale food and drug toxicity tests because the following reasons. (1) They have transparent embryos that make the organogenesis are easy to observe; (2) One pair of adult fish is capable of laying 200–300 eggs per week; (3) The zebrafish genome project is almost completed. In this thesis, we design many screening methods, such as mobility test and kidney morphology for food and drug toxicity tests using sodium benzoate, caffeine, cisplatin and ruthenium complex as positive controls. Results showed that zebrafish embryos displayed lower swimming mobility after exposure to 10 ppm of sodium benzoate but had no swimming ablity after exposure to 2000 ppm of sodium benzoate. With regards to kidney toxicities, the threshold for the sodium benzoate, caffeine, cisplatin and ruthenium complex are 500, 75, 20 and 75 ppm, respectively. In conclusion, these screening methods are excellent and effective for large-scale food and drug toxicity screening, especially for nephrotoxicities.

目錄

中文摘要  ------------------------------------- I
英文摘要  ------------------------------------- II
中英文對照表  --------------------------------- III
目錄  ----------------------------------------- IV
圖表目錄  ------------------------------------- VI 


第一章 前言	............................. 1
第二章 材料與方法	............................. 8
2.1 實驗材料  ................................. 8
2.2 實驗方法  ................................. 9
第三章 結果  .................................. 14
3.1 浸泡苯甲酸鈉之能動性測試 .................. 14
3.2浸泡苯甲酸鈉後在斑馬魚腎臟毒性測試 ......... 15
3.3 浸泡咖啡因後在斑馬魚腎臟毒性測試	........... 17
3.4 浸泡順鉑金屬化合物後在斑馬魚腎臟毒性的表現 . 20 
3.5浸泡釕金屬化合物後在斑馬魚腎臟毒性的表現 .... 21
第四章 討論 .................................... 23
4.1 斑馬魚與生物體外之新藥開發篩選 ............. 23
4.2 斑馬魚與哺乳動物的腎臟構造 ................. 24
4.3 斑馬魚與哺乳動物的成本比較 ................. 25
4.4 觀察斑馬魚行為變異情形 ..................... 26
4.5 腎臟綠螢光基因轉殖斑馬魚之優勢 ............. 26
4.6 總結 ....................................... 28

圖表目錄


圖一 各種不同時期的斑馬魚之食品與藥物的浸泡方式 ------ 33
圖二 食品與藥物對斑馬魚之毒性測試項目 ---------------- 34
圖三 浸泡SB後各種毒性測試 --------------------------- 35
圖四 浸泡咖啡因後使身體變短之統計圖 ------------------ 36
圖五 浸泡苯甲酸鈉和咖啡因的腎臟變異情形 ( Method I ) - 37
圖六 浸泡順鉑和釕金屬的腎臟變異情形 ( Method I ) ----- 38
圖七 浸泡苯甲酸鈉和咖啡因的腎臟變異情形( Method VI ) - 39
圖八 浸泡順鉑和釕金屬的腎臟變異情形( Method VI ) ----- 40
附錄圖一 --------------------------------------------- 41
附錄圖二 --------------------------------------------- 42
著作目錄 --------------------------------------------- 43
期刊論文一 ------------------------------------------- 44
期刊論文二 ------------------------------------------- 52
期刊論文三 ------------------------------------------- 60

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