近年來，含有馬兜鈴酸 (AA)中草藥對健康影響的爭議不斷，報導有多起腎纖維化和腎衰竭的案例皆與病人服用中藥有關。本研究提出新穎的檢測馬兜鈴酸I (AAI)的生化檢測方法，使用具有表面增強拉曼散射 (SERS)的銀奈米粒子(Ag NPs)和具有螢光的環氧樹脂奈米點 (Epoxy NDs)，分別作為SERS和螢光 (PL)光譜檢測AAI的基材。
在SERS的實驗中，會形成兩種類型的複合物：一為AAI結合於3-氨基丙基雜氮矽三環 (APS)包覆的Ag NPs。銀離子還原成粒徑為5.48 ± 0.14 nm的球型Ag NPs，形成APS層後產生更大且粒徑為4.78 ± 0.09 μm的聚集體，最後AAI包覆在APS上而形成AAI/APS@AgNPs。在此，APS不只作為還原劑，還作為包覆劑；另一為AAI直接和Ag NPs結合，再使用APS包覆在外層而形成APS/AAI@AgNPs。透過X-ray光電子能譜 (XPS)和傅立葉轉換紅外光譜 (FTIR)證實Ag NPs的合成機制，還透過XPS和能量分散光譜 (EDS)證實Ag NPs的還原，且透過SERS來探討Ag NPs還原的最佳條件，並測得高達10⁵數量級的增強因子 (EF)，且其SERS的偵測極限 (Limit of detection；LOD)為10 μM。
而在PL的實驗中，修飾已硝基還原化後AAI在Epoxy NDs的表面上是進行胺解反應，並有助於提高螢光強度。透過XPS和FTIR證實Epoxy NDs和AAI的修飾位置，還透過PL來探討Epoxy NDs和AAI反應的最佳條件，且其PL的LOD為2 μM。
AAI在體內會被代謝成馬兜鈴內醯胺Ia (ALIa)，本研究用於檢測ALIa的兩種生化檢測方法，不只易於製備，成本低廉，還不用繁瑣的樣品前處理等，可能為臨床研究中的現有檢測ALIa的檢測方法中，提供卓越的替代方案。

Controversy over the health effects of Chinese herbal medicines containing aristolochic acid remains unresolved. Multiple cases of renal fibrosis and renal failure have been reported in patients taking Chinese medicines. In this study, a novel biochemical method for the detection of Aristolochic acid I (AAI) is proposed. We used silver nanoparticles (Ag NPs) for surface enhanced Raman scattering (SERS) and fluorescent Epoxy nanodots (Epoxy NDs), as substrates for detection of AAI by SERS and Photoluminescence (PL) spectra respectively.
For SERS experiments, two types of complexes were formed. In the first, AAI was bound to 3-Aminopropylsilatrane (APS) coated Ag NPs. Silver ions were reduced to form spherical (5.48 ± 0.14 nm) Ag NPs, then an APS layer was formed, creating a large aggregate (4.78 ± 0.09 μm) and finally AAI was coated on the APS to form AAI/APS@Ag NPs. Here, APS was not only used as a reducing agent, but also a coating agent. In the second method, AAI was directly bound to the Ag NPs and then an outer coating of APS was applied to form APS/AAI@Ag NPs. The proposed mechanism for Ag NPs synthesis was confirmed by X-ray photoelectron spectra (XPS) and Fourier transform infrared (FTIR). The reduction of Ag NPs was confirmed by XPS and Energy-dispersive X-ray spectra (EDS). We investigated the best reducting conditions of Ag NPs by SERS, and measured the enhancement factor of up to 10⁵. The limit of detection (LOD) of SERS is 10 μM.
For PL experiment, the modified nitroreducted AAI underwent aminolysis reaction on the surface of Epoxy NDs, which served to enhance the fluorescence intensity. The modification of Epoxy NDs was confirmed by XPS and FTIR. The LOD of PL is 2 μM.
In the body, AAI is metabolized to form Aristololactam Ia (ALIa). The two biochemical methods demonstrated in this study for detecting ALIa are easily prepared, economical, and don’t require complicated pretreatment of the samples. These may provide a superior alternative to existing detection methods for ALIa in clinical studies.

摘要 i
Abstract ii
目錄 iv
圖次 viii
表次 xii
第壹章 緒論 1
1-1 馬兜鈴酸 (Aristolochic acid) 1
1-2 研究動機 5
第貳章 儀器原理 6
2-1 拉曼光譜儀 (Raman spectrometer) 6
2-1-1 簡介 6
2-1-2 參數設定及樣品製備 10
2-2 光致發光光譜儀 (Photoluminescence spectrometer) 11
2-2-1 簡介 11
2-2-2 參數設定及樣品製備 13
2-3 X-ray光電子能譜儀 (X-ray photoelectron spectrometer) 14
2-3-1 簡介 14
2-3-2 參數設定及樣品製備 15
2-4 傅立葉轉換紅外光譜儀 (Fourier transform infared spectrometer) 16
2-4-1 簡介 16
2-4-2 參數設定及樣品製備 17
2-5 紫外光/可見光譜儀 (Ultraviolet-visble spectrometer) 18
2-5-1 簡介 18
2-5-2 參數設定及樣品製備 19
2-6 掃描式電子顯微鏡 (Scanning electron microscope) 20
2-6-1 簡介 20
2-6-2 參數設定及樣品製備 21
2-7 穿透式電子顯微鏡 (Transmission electron microscope) 22
2-7-1 簡介 22
2-7-2 參數設定及樣品製備 23
2-8 能量分散光譜儀 (Energy dispersive spectrometer) 24
2-8-1 簡介 24
2-8-2 參數設定及樣品製備 25
第叁章 以表面增強拉曼散射 (SERS)光譜分析馬兜鈴酸I的研究 26
3-1 前言 26
3-2 文獻回顧─表面增強拉曼散射 (SERS)機制 28
3-3 實驗部分 32
3-3-1 實驗藥品 32
3-3-2 實驗流程 32
3-4 實驗結果 36
3-4-1 鑑定銀奈米粒子 (Ag NPs)的還原 36
3-4-2 鑑定APS/AAI@Ag NPs的形成 39
3-4-3 推測APS/AAI@Ag NPs可能的合成位置 44
3-4-4 APS/AAI@Ag NPs的合成機制 51
3-4-5 比較APS/AAI@Ag NPs和AAI/APS@Ag NPs的差異 52
3-4-6 探討Ag NPs還原的最佳條件 56
3-4-7 探討3-氨基丙基雜氮矽三環 (APS)包覆量的關係 59
3-4-8 以表面增強拉曼散射 (SERS)光譜分析AAI的偵測極限 61
3-4-9 此SERS光譜檢測AAI研究和其他文獻比較的優勢 63
3-4-10 結論 65
第肆章 以螢光 (PL)光譜分析馬兜鈴酸I的研究 66
4-1 前言 66
4-2 文獻回顧─光致發光 (PL)機制 68
4-3 實驗部分 71
4-3-1 實驗藥品 71
4-3-2 實驗流程 71
4-4 實驗結果 73
4-4-1 探討所合成的環氧樹脂奈米點 (Epoxy NDs)的特徵分析 73
4-4-2 推測馬兜鈴酸I (AAI)修飾在Epoxy NDs的可能位置 75
4-4-4 AAI修飾在Epoxy NDs上的機制 79
4-4-5 選定Epoxy NDs的激發波長 81
4-4-6 探討Epoxy NDs和AAI反應的最佳條件 82
4-4-7 以螢光 (PL)光譜分析AAI的偵測極限 83
4-4-8 此PL光譜檢測AAI研究和其他文獻比較的優勢 85
4-4-9 結論 88
第伍章 實際應用於尿液檢體的檢測 89
5-1 前言 89
5-2 文獻回顧─馬兜鈴酸 (AA)的致癌原因 91
5-3 實驗部分 93
5-3-1 實驗藥品 93
5-3-2 實驗流程 94
5-4 實驗結果 98
5-4-1 探討馬兜鈴酸I (AAI)在正常尿液中的檢測情形 98
5-4-2 以表面增強拉曼散射 (SERS)檢測尿液檢體 99
5-4-3 結論 100
第陸章 總結 101
第柒章 參考文獻 102

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