為提升食品營養價值非法添加化學物於食品中，已經造成全球食品恐慌，其中
一個例子為 2007 年上半年，美國發生多起寵物食用特定廠牌之飼料後，在腎臟產
生結石引發急性腎衰竭而死亡的案例，而類似事件也發生在 2008 年由中國大陸所
生產之奶粉，造成多起嬰兒死亡。傳統以凱氏定氮法評估食品中之氮含量，因此有
不肖廠商添加三聚氰胺在奶粉及寵物飼料中，意圖非法提升其氮含量，此非法添加
物會引發急性腎衰竭甚至死亡。由先前文獻報導可得知造成急性腎衰竭的原因，是
因為三聚氰胺所誘導而產生之結石，會阻礙腎小管之水份運送，尤其對腎臟尚未發
展完全之初生嬰兒更為嚴重。傳統探討動物腎臟中三聚氰胺的分析方法為萃取組織
中之三聚氰胺，再經由液相層析法分離，質譜儀或是 UV 偵測器偵測，即可得知三
聚氰胺在組織中之含量，但經過這些均質 (Homogenization) 步驟，並沒有辦法直接
觀察腎臟中三聚氰胺之分布狀況。
基質輔助雷射脫附游離結合影像質譜法 (Matrix-Assisted Laser
Desorption/Ionization Imaging Mass Spectrometry, MALDI-IMS) 已經被證明可提供
分析物中各類化學物質分布之訊息，本研究利用 MALDI-IMS 研究三聚氰胺在老鼠
腎臟及肝臟中空間之分布。根據分子影像結果，單獨餵食三聚氰胺之大鼠腎臟，三
聚氰胺之訊號集中於腎盂 (Pelvis)，而在同時餵食三聚氰胺及三聚氰酸之大鼠腎
臟，可觀察到三聚氰胺大量累積在腎臟三個主要區域 [皮質 (Cortex)、髓質 (Medulla)
以及腎盂]。除了腎臟組織，在肝臟組織也有發現三聚氰胺之訊號，但並無觀察到累
積之現象。以組織學染色方式觀察腎臟以及肝臟組織，在同時餵食三聚氰胺以及三
聚氰酸之腎臟組織中可觀察到結石之影像。利用雷射顯微細胞組織擷取系統 (Laser
Micro-Dissection System, LMD) 將腎臟組織中的結石擷取至容器中，分析後可得知
結石中含有三聚氰胺以及三聚氰酸。
除了觀察三聚氰胺之訊號分布外，亦觀察在餵食不同藥物後脂質之變化，從分
子影像中可以得知，結石的存在與脂質之變化並無明顯之相關性，只有在單獨餵食
三聚氰酸之大鼠腎臟中，脂質之訊號有明顯降低之趨勢，可能原因為餵食大鼠三聚
氰酸會造成腎臟實質 (Parenchyma) 之部分營養不良 (Dystrophic)，所以脂質之訊號
會較其它餵食組別低。

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目錄
論文摘要 I
目錄 III
圖目錄 VI
壹、 緒論 1
一、 前言 1
二、 影像質譜結合基質輔助雷射脫附游離法 3
1、 基質輔助雷射脫附游離法之原理 3
2、 影像質譜結合基質輔助雷射脫附游離法 5
三、 三聚氰胺與三聚氰酸 22
1、 三聚氰胺 22
2、 三聚氰酸 23
3、 當三聚氰胺遇到三聚氰酸 24
四、 腎臟與肝臟 25
1、 腎臟 25
2、 肝臟 26
五、 論文目標 28
貳、 實驗部份 29
一、 儀器 29
1、 質譜儀 (Mass spectrometer)： 29
2、 冷凍切片機 (Cryostat Chamber) 29
3、 噴槍 (Air Brush)： 29
4、 雷射顯微細胞組織擷取系統 (Laser Micro-Dissection System, LMD) 30
5、 超音波震盪器 30
二、 化學試劑 30
1、 MALDI 基質 30
2、 溶劑 30
3、 藥品 30
4、 MALDI 基質溶液配製方法 31
5、 標準品溶液配製 31
6、 動物 31
三、 動物組織 32
四、 基質塗附 33
參、 結果與討論 34
一、 基礎條件探討 34
二、 利用Profiling與染色法確認實驗設計結果 42
1、 尿液樣品 42
2、 組織染色結果 44
3、 大鼠腎臟組織之profiling 47
三、 影像質譜結果 56
1、 腎臟之影像質譜 56
2、 肝臟之影像質譜 64
肆、 結論 69
伍、 參考文獻 70
陸、 附錄 75

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