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研究生:吳伊婷
研究生(外文):Yi-Ting Wu
論文名稱:Sulfasalazine對於同半胱胺酸代謝之影響
論文名稱(外文):The effects of sulfasalazine on homocysteine metabolism
指導教授:蔣恩沛
指導教授(外文):En-Pei Chiang
學位類別:碩士
校院名稱:國立中興大學
系所名稱:食品暨應用生物科技學系所
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
畢業學年度:98
語文別:英文
論文頁數:55
中文關鍵詞:硫-腺核苷甲硫胺酸甲硫胺酸硫腺核苷轉移酶
外文關鍵詞:SulfasalazineS-adenosylmethionineMethionine adenosyltransferase
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中文摘要
背景: Sulfasalazine,其抗發炎的機制為促進局部發炎組織其嘌呤核苷酸 (adenosine) 的釋出,而此作用則會造成三磷酸腺苷 (adenosine triphosphate, ATP) 的減少。三磷酸腺苷為合成硫-腺核苷甲硫胺酸之 (S-adenosylmethionine, adoMet) 前驅物,我們推測其含量降低可能會導致硫-腺核苷甲硫胺酸之合成也減少以及造成後續DNA 的低度甲基化。
本篇研究的目的則是要去探討是否sulfasalazine會直接地影響不同組織中硫-腺核苷甲硫胺酸的含量以及DNA 整體甲基化的程度。
實驗設計與方法: 以橫斷式研究法調查了台灣台中榮民總醫院免疫風濕科共133位罹患類風濕性關節炎之受測者; 並同時進行了動物實驗,分析與轉甲基作用有關的生化數值。分析其血液中同半胱胺酸及其相關的代謝物如葉酸、硫-腺核苷甲硫胺酸、硫-腺核苷同半胱胺酸之濃度,並測量了不同組織中硫-腺核苷甲硫胺酸合成酶之酵素活性。
結果: 服用sulfasalazine的病人其全血中硫-腺核苷甲硫胺酸的濃度增高了778%,而且sulfasalazine之劑量或服藥期間長短皆與全血中的硫-腺核苷甲硫胺酸成正相關。動物實驗顯示,sulfasalazine 顯著地改變不同組織中硫-腺核苷甲硫胺酸之含量。同樣地,負責合成硫-腺核苷甲硫胺酸之酵素在小鼠的不同組織中也觀察到不同地結果。
結論: Sulfasalazine 對於不同組織中硫-腺核苷甲硫胺酸的含量與合成酵素皆有不同的影響。
Contents
中文摘要…………………………………………………………………………………i
ABSTRACT………………………………………………………………………….....ii
List of abbreviations………………………………………......………………………iv
Part I
INTRODUCTION…………………………………………………………………….1
MATERIALS AND METHODS………………………………………………………4
RESULTS……………………………………………………………………………....11
DISCUSSION………………………………………………………………………….17
TABLES
Table 1. Demographic data………………...…………………………………………26
Table 2. Concentrations of the metabolites and related enzyme activity……….…27
Table 3. Correlation between indices of methylation status in human.……………28
Table 4. Effects of Sulfasalazine treatment on AdoMet and AdoHcy in vivo……...29
Table 5. Effects of Sulfasalazine treatment on MAT activity in vivo…………….…32
Table 6. Correlations between indices of methylation status in vivo……………….33
Table 7. Effects of Sulfasalazine treatment on Hcy, Cys, AdoMet and AdoHcy concentrations in response to a methionine load in vivo……………………………36
Table 8. Effects of Sulfasalazine treatment on dMC% in vivo…..…………………37
FIGURES
Figure 1. HPLC chromatography in patients with rheumatoid arthritis………….22
Figure 2. The relationships between adoMet and sulfasalazine……………………24
Figure 3. Potential mechanisms linking methylation indices in patients receiving sulfasalazine…………………………………………………………………………...35
Part II
Table 1. Effects of Prednisolone treatment on folate status………………………...40
Table 2. Effects of Prednisolone treatment on folate dependent remethylation…..42
Table 3. Effects of Prednisolone treatment on homocysteine remethylation in kidney…………………………………………………………………………………..44
Table 4. Effects of Prednisolone treatment on AdoMet and AdoHcy in vivo……...47
Table 5. Effects of Prednisolone treatment on Hcy and Cys concentrations in response to a methionine load in vivo………………………………………………..48
Table 6. Effects of Prednisolone treatment on Liver………………………………..49
Table 7. Effects of Prednisolone treatment on Bone Marrow…………………..…..50
Reference list…..............................................................................................................51
Reference List

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