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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 黃青真 | |
dc.contributor.author | Yi-Jen Li | en |
dc.contributor.author | 李亦臻 | zh_TW |
dc.date.accessioned | 2021-06-15T00:14:29Z | - |
dc.date.available | 2019-06-26 | |
dc.date.copyright | 2009-06-30 | |
dc.date.issued | 2009 | |
dc.date.submitted | 2009-06-26 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41224 | - |
dc.description.abstract | 近年發現 2,5,7,8-tetramethyl-2-(2’-carboxyethyl)-6-hydroxychroman (alpha-CEHC) 為維生素 E 側鏈被切短後的水溶性代謝產物。目前推測其側鏈截短之代謝途徑牽涉到 omega-hydroxylation 及支鏈 beta-oxidation。由於催化 omega-hydroxylation 之酵素 cytochrome P450 4A1 (CYP4A1) 及過氧化體 beta-oxidation 的酵素 acyl-CoA oxidase 1 (ACO1) 均為受 peroxisome proliferator-activated receptor alpha (PPARalpha) 調控之下游基因。為探討 PPARalpha 對維生素 E 代謝生成 alpha-CEHC 之影響效應,本研究以大鼠之動物模式,投予 PPARalpha 活化劑 clofibrate 及 perfluorodecanoic acid (PFDA) 誘發 PPARalpha 標的基因表現,觀察活化 PPARalpha 傳訊途徑對鼠尿中維生素 E 代謝產物 alpha-CEHC 排出量之影響。
alpha-CEHC 於體內會與 glucuronic acid 或 sulfate 等結合,形成alpha-CEHC conjugate,隨尿液排出體外。文獻分析樣品 alpha-CEHC之方法,多用 beta-glucuronidase 酵素水解 alpha-CEHC conjugates,再以 high performance liquid chromatography with electrochemical detector (HPLC-ECD) 定量之。然而,本實驗發現鼠尿經 HCl 強酸處理後,HPLC-ECD 所測得之 alpha-CEHC 含量會明顯竄升,以 beta-glucuronidase 酵素處理者則否。為確認鼠尿 alpha-CEHC conjugate之結構,我們將鼠尿進行純化分離,經化學結構鑑定確認此HCl releasable alpha-CEHC conjugate為 6-O-sulfated alpha-CEHC (alpha-CEHC sulfate)。另外,我們亦重建酸水解萃取分析尿液 conjugated alpha-CEHC 之方法:將含抗壞血酸之樣品,以 6 N HCl 於 60度C 反應 1 小時進行酸加熱水解,之後以乙醚萃取,續以 HPLC-ECD 進行 alpha-CEHC 定量分析。在熱酸水解過程中,以抗壞血酸作為抗氧化劑可以有效地保護 alpha-CEHC不被破壞。此分析方法的優點為快速、靈敏及回收率佳。 動物實驗共分三部分進行。實驗一採雙因子變因設計,分別給予大鼠餵食含 50 mg/kg all-rac-alpha-tocopheryl acetate (alpha-TA) (L 組)、50 mg/kg alpha-TA + 0.5% clofibrate ( LC 組)、500 mg/kg alpha-TA (H 組) 或 500 mg/kg alpha-TA + 0.5% clofibrate ( HC 組) 之試驗飼料為期一週,其間並收集尿液。結果顯示 clofibrate 處理會造成大鼠肝臟及血清 alpha-tocopherol (alpha-TOH) 含量明顯下降及肝臟中 PPARalpha 下游基因 ACO1、CYP4A1 及 D-bifunctional protein (D-BF) 之酵素活性、蛋白質或 m-RNA 表現量顯著增加。尿液 alpha-CEHC 排出量方面,LC 組老鼠之每日 alpha-CEHC 排出量顯著高於 L 組老鼠 (p<0.05),HC 組卻稍低於 H 組。若將 alpha-CEHC 排出量以佔每日飲食維生素 E 攝入量的比例來表示,可以發現LC 組老鼠之 alpha-CEHC 排出量顯著高於 L 組 (p<0.05),HC 組老鼠之 alpha-CEHC 排出量略高於 H 組,但組間無統計差異。 延續實驗一之結果,實驗二改以管餵方式提供正常劑量之維生素 E (5 mg alpha-TA/kg B.W./day),觀察給予含 0 (C 組)、0.1 % (0.1P 組)、0.25% (0.25P 組)、0.5% (0.5P 組) 或 1 % (1P 組) 之 clofibrate 試驗飼料一週,對維生素E代謝之影響。結果顯示,clofibrate 處理會造成 PPARalpha 標的基因 ACO1、CYP4A1及參與支鏈脂肪酸代謝之 ACO2 及 D-BF 等之酵素活性、蛋白質或 mRNA 表現量顯著增加,且具劑量效應之趨勢。尿液中每日 alpha-CEHC 排出量亦隨 clofibrate 處理劑量增加而上升。且 ACO1、CYP4A1、ACO2 及 D-BF之表現與尿液alpha-CEHC 排出量呈顯著之正相關性 (r=0.30-0.46, p<0.05)。 實驗三則在正常維生素 E 劑量 (50 mg alpha-TA/kg diet) 試驗飼料下,每日以腹腔方式給予 0、0.5、1、2.5、5 或 10 mg/kg B.W. 之 PFDA,誘發 PPARalpha 傳訊途徑,觀察不同類型之 PPARalpha 活化劑對維生素E代謝之影響。結果顯示,PFDA 同樣會造成 PPARalpha 下游基因 ACO1、CYP4A1等之酵素活性、蛋白質或 m-RNA 表現量顯著增加,且具劑量效應。尿液中每日 alpha-CEHC 排出量亦隨 PFDA 處理劑量增加而上升。PPARalpha 下游基因 ACO1、CYP4A1之表現與尿液alpha-CEHC 排出量呈顯著之正相關 (r=0.40-0.56, p<0.05)。至於,目前文獻中提及可能參與維生素 E 代謝之相關蛋白質,如 CYP3A、CYP4F等,於本實驗中其 mRNA或蛋白質表現量與尿液 alpha-CEHC 排出量無關聯性,甚至呈負相關。 因此,本研究之結果初步證實利用 PPARalpha 活化劑 clofibrate 及 PFDA 誘發 PPARalpha 標的基因的表現,會促進體內維生素 E代 謝,增加尿液中 alpha-CEHC 的排出量。活化 PPARalpha 傳訊途徑可能會影響體內維生素 E 的代謝。 | zh_TW |
dc.description.abstract | 2,5,7,8-tetramethyl-2-(2’-carboxyethyl)-6-hydroxychroman (alpha-CEHC), the metabolite of alpha-tocopherol (alpha-TOH) with a shortened side chain but an intact hydroxychroman structure, has been identified in the urine. Pathway of the metabolism involves omega-hydroxylation of phytyl side chain and the following beta-oxidation. omega-Hydroxylation is known to be catalyzed by cytochrome P450 enzymes (CYPs), of which CYP3A and CYP4F is the most likely candidates. The enzymes which are responsible for the omega-oxidation (CYP4A1) and peroxisomal beta-oxdiation (acyl-CoA oxidase 1, ACO1) of fatty acid are transcriptionally regulated by peroxisome proliferator activated receptor alpha (PPARalpha). In order to investigate effects of PPARalpha activation on the vitamin E metabolism, Wistar rats were treated with PPARalpha activators - clofibrate and perfluorodecanoic acid (PFDA) and urinary alpha-CEHC was monitored in this study.
alpha-CEHC was known to be conjugated with glucuronic acid or sulfate. Various CEHCs in biological specimen were mostly measured by high performance liquid chromatography with electrochemical detector (HPLC-ECD) preceded by beta-glucuronidase hydrolysis. In an attempt to analyze alpha-CEHC in rat urine accordingly, it observed that enzyme hydrolysis was relatively inefficient in releasing alpha-CEHC compared to high concentrations of HCl. The HCl releasable alpha-CEHC conjugate was therefore isolated and chemically identified as 6-O-sulfated alpha-CEHC (alpha-CEHC sulfate). Using the synthetic alpha-CEHC sulfate standard, it was found that sulfatase could not hydrolyze to a significant extent. On the other hand, pretreatment with HCl at 60。C in the presence of ascorbate, followed by a one-step ether extraction not only hydrolyzed the sulfate conjugate completely but also extracted alpha-CEHC with high recovery. The inclusion of ascorbate minimized the conversion of alpha-CEHC to alpha-tocopheronolactone in the HCl pretreatment. A complete procedure for the quantitative analysis of alpha-CEHC including HCl hydrolysis, ether extraction and reverse phase isocratic HPLC-ECD was thus established. A total of three rat experiments were conducted to examine the effects of PPARalpha activators on urinary alpha-CEHC excretion. In Experiment 1, rats were fed diets containing 50 mg/kg all-rac-alpha-tocopheryl acetate (alpha-TA) (L), 50 mg/kg alpha-TA + 0.5% clofibrate ( LC ), 500 mg/kg alpha-TA (H) or 500 mg/kg alpha-TA + 0.5%clofibrate (HC) for 1 week, and the urine was collected for alpha-CEHC analysis. PPARalpha target genes including CYP4A1, ACO1 and D-BF is induced significantly by clofibrate revealed by the expression of enzyme activity, protein or mRNA. Clofibrate treatment resulted in a significant decrease of the alpha-TOH content in serum and liver. The urinary alpha-CEHC content of LC group is significantly higher than that of the L group (p<0.05). The ratio of urinary alpha-CEHC to dietary vitamin E intake of the LC group is also significantly higher than the L group. However, no significant difference between H and HC group was found. In Experiment 2, rats were fed vitamin E devoid AIN-76 modified diets containing 0 (C), 0.1 (0.1CF), 0.25 (0.25CF), 0.5 (0.5CF), 1 (1CF) % clofibrate and were i.p. injected with 5 mg alpha-TA/kg B.W. daily for 1 week. Expressions of PPARalpha target genes, namely, CYP4A1, ACO1, ACO2 and D-BF that participated in the metabolism of fatty acid were all increased significantly and does-dependently by the clofibrate treatment as revealed by the of enzyme activity, protein or mRNA expression. The urinary alpha-CEHC excretion of all clofibrate treated groups were also increased does-dependently (p<0.05). Again, there were significantly positive correlations between the urinary alpha-CEHC and the expression of CYP450, CYP4A1 and ACO1 (r=0.40-0.56, p<0.05). In Experiment 3, another PPARalpha activator PFDA was used. All of the 6 groups of rats were fed the AIN-76 modified diet containing 50 mg/kg alpha-TA and respectively tube-fed vehicle (C) or 0.5 (0.5P), 1(1P), 2.5 (2.5P), 5 (5P) or 10 (10P) mg/kg body weight of PFDA daily for 1 week. PPARalpha target genes - CYP4A1 and ACO1 expression in the liver also increased significantly and does-dependently by PFDA as revealed by enzyme activity, protein or mRNA expression (p<0.05). The urinary alpha-CEHC content of all PFDA treated groups also increased does-dependently (p<0.05). Positive correlations between the urinary alpha-CEHC and the expression of CYP4A1 and ACO1 were again observed (r=0.42-0.50, p<0.05). However, CYP3A and CYP4F which has been considered to catalyze vitamin E catabolism to alpha-CEHC showed no correlation with urinary alpha-CEHC in this study (p>0.05). In conclusion, this study demonstrates that PPARalpha activation is associated with an increased urinary alpha-CEHC excretion. The activation of PPARalpha signal pathway may enhance the vitamin E catabolism through up-regulation of some of its target genes (ex. CYP4A1 and ACO1). | en |
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dc.description.tableofcontents | 目 錄
中文摘要i 英文摘要iii 縮寫對照表v 第一章 緒言1 第一節 研究動機與目的1 第二節 文獻回顧2 一、維生素 E 簡介2 二、維生素 E 的吸收、運轉與分佈4 三、維生素 E的生理功能 7 四、維生素 E 的抗氧化代謝產物 8 五、維生素 E的非抗氧化代謝產物 CEHCs 11 六、過氧化體增殖劑活化受器 (PPAR) 29 七、Xenobiotics 代謝 33 第三節 實驗假說與研究架構 40 一、實驗假說 40 二、研究架構 40 第二章 鼠尿 alpha-CEHC sulfate 純化鑑定與 conjugated alpha-CEHC分析方法之重建 41 第一節 前言 41 第二節 材料方法 43 一、化學藥品及試劑配製 43 二、鼠尿及人尿樣品 44 三、Conjugated alpha-CEHC 之不同水解方式及其萃取步驟 45 四、HPLC 分析 48 五、分離、純化與鑑定 51 六、統計分析 54 第三節 結果 55 一、HCl 酸水解對鼠尿 alpha-CEHC 含量分析結果之影響 55 二、鼠尿經 HCl水解後於 HPLC-ECD 分析中所得 alpha-CEHC 波峰之成分確認 55 三、鼠尿中 HCl-releasable alpha-CEHC conjugate 之分離、純化與鑑定58 四、以酸水解分析尿液 alpha-CEHC 條件之再確認 65 五、比較人尿與鼠尿 alpha-CEHC conjugates 之異同 80 第四節 討論與結論 82 一、鼠尿 alpha-CEHC conjugates 之型式 82 二、Sulfatase 酵素無法有效地水解 alpha-CEHC sulfate 83 三、Ascorbic acid 可以有效抑制 alpha-CEHC 生成 alpha-tocopheronolactone83 四、Free alpha-CEHC 與 total alpha-CEHC 的關聯性 84 五、維生素 E 的代謝與 sulfation 84 六、結論 85 第三章 降血脂藥物 clofibrate 對維生素 E代謝生成 alpha-CEHC 之影86 第一節 前言 86 第二節 材料與方法 88 一、實驗大綱 88 二、試驗飼料的配製 90 三、動物飼養 90 四、尿液收集 93 五、動物犧牲及組織樣品收集 93 六、血液脂質分析 93 七、肝臟脂質分析 95 八、血清及肝臟之 alpha-tocopherol 含量分析 96 九、尿液 alpha-CEHC 含量分析 98 十、尿液 creatinine 含量分析 98 十一、肝臟 CYP450 總含量分析 99 十二、肝臟過氧化體 ACO1 活性分析 101 十三、以西方轉漬法分析肝臟 ACO1 及 CYP4A1 蛋白質含量 105 十四、以北方轉漬法分析肝臟 PPARalpha 下游基因之 mRNA 表現量 109 十五、統計分析 115 第三節 結果 116 一、生長狀況 116 二、血清及肝臟脂質含量 119 三、血清及肝臟 alpha-tocopherol 含量 120 四、尿液 alpha-CEHC 排出量 124 五、飲食維生素 E 攝入量與尿液 alpha-CEHC 排出量之關係 125 六、肝臟微粒體 CYP450 總含量 130 七、肝臟過氧化體 ACO1活性 130 八、肝臟 CYP4A1 及 ACO1 蛋白質表現量 133 九、肝臟 PPARalpha 傳訊途徑相關之基因 mRNA 表現量 133 十、尿液 alpha-CEHC 排出量與維生素 E 攝入量、血清及肝臟 alpha-tocopherol 含量之相關性分析 138 十一、 尿液 alpha-CEHC 排出量與clofibrate 劑量、肝臟 CYP450含量及PPARalpha 下游基因ACO 、CYP4A1 等之活性、蛋白質或 mRNA表現量之相關性分析 138 第四節 討論與結論 143 一、Clofibrate 對動物生長狀況之影響效應 143 二、Clofibrate 對 PPARalpha 標的基因及參與脂肪酸代謝相關基因之影響143 三、飲食維生素 E 含量對體內維生素 E 含量及尿液 alpha-CEHC 排出量之影響 144 四、活化 PPARalpha 傳訊途徑對體內維生素 E 含量及尿液 alpha-CEHC 排出量之影響 145 五、PPARalpha 傳訊途徑與維生素 E 代謝生成 alpha-CEHC 之關聯性 147 六、維生素 E 對 PPARalpha 及其標的基因之影響 147 七、結論 149 第四章 環境污染物 PFDA 對維生素 E 代謝生成 alpha-CEHC 之影150 第一節 前言 150 第二節 材料與方法 152 一、實驗大綱 152 二、試驗飼料的配製 153 三、動物飼養 153 四、尿液收集 154 五、動物犧牲及樣品收集 154 六、血液脂質分析 154 七、肝臟脂質分析 154 八、血漿、肝臟及脂肪組織之 alpha-tocopherol 含量分析 154 九、尿液、血清及肝臟總 alpha-CEHC 含量分析 155 十、肝臟 CYP450 總含量分析 155 十一、肝臟過氧化體 ACO1 活性分析 156 十二、以西方轉漬法分析 ACO1, CYP4A1 及 CYP3A1/2 蛋白質含量156 十三、以 Real-time PCR分析 PPARalpha 及 PXR下游基因等之 mRNA 表現量156 十四、統計分析158 第三節 結果 159 一、生長狀況 159 二、血清及肝臟脂質含量 162 四、尿液 alpha-CEHC 排出量 166 五、血清及肝臟 alpha-CEHC 含量 166 六、肝臟微粒體 CYP450 總含量 173 七、肝臟微粒體各CYP 蛋白質表現量 173 八、肝臟過氧化體 ACO1 酵素活性及蛋白質表現量 174 九、肝臟中與 PPAR alpha 及脂肪酸代謝相關基因之 mRNA 表現量 178 十、肝臟中與維生素 E 代謝相關基因之 mRNA 表現量 179 十一、 尿液 alpha-CEHC 排出量與肝臟 CYPP450含量、PPARalpha 或脂肪酸代謝相關基因等之活性、蛋白質或 mRNA表現量之相關性分析181 十二、 尿液 alpha-CEHC 排出量與已知可能參與維生素 E 相關代謝蛋白質之相關性分析 181 第四節 討論與結論 184 一、PFDA 對動物生長狀況之影響效應 184 二、PFDA 對體內脂質代謝之影響 184 三、PFDA 對 PPARalpha 標的基因及參與脂肪酸代謝相關基因之影響185 四、PFDA 對體內維生素 E 及 alpha-CEHC 含量之影響 185 五、PFDA 對參與維生素 E 相關代謝蛋白質之影響 186 六、PPARalpha 傳訊途徑與維生素 E 代謝生成 alpha-CEHC 之關聯性 189 七、結論 190 第五章 綜合討論與總結論 191 第六章 參考文獻 196 附錄206 圖目錄 圖 1-1 維生素 E 的化學結構2 圖 1-2 維生素 E 與自由基反應之代謝途徑及其產物9 圖 1-3 Simon’s 代謝物10 圖 1-4 維生素 E 之可能代謝途徑 14 圖 1-5 PPAR/RXR 之活化機制30 圖 1-6 粒線體與過氧化體之脂肪酸 beta-oxidation 33 圖 1-7 UDPGT 催化之 glucuronidation 反應36 圖 1-8 SULT 催化之 sulfation 反應37 圖 1-9 維生素 E 與 xenobiotics 代謝之相互作用39 圖 2-1 鼠尿經酵素或酸水解處理後之 HPLC-ECD 層析圖56 圖 2-2 以製備式 RP-18 HPLC 純化鼠尿經酸處理之 alpha-CEHC 目標產物及其成分鑑定 57 圖 2-3 鼠尿 HCl-releasable alpha-CEHC conjugates 之純化流程與 HPLC 層析圖61 圖 2-4 鼠尿 conjugated alpha-CEHC (6-O-sulfated alpha-CEHC) 之成分鑑定 63 圖 2-5 HCl 添加劑量 (A) 與 pH 值 (B) 對大鼠尿液之 alpha-CEHC 與 alpha-tocopheronolactone 測定值之影響70 圖 2-6 HCl添加劑量 (A) 與 pH 值 (B) 對 alpha-CEHC sulfate 標準品溶液之 alpha-CEHC 與 alpha-tocopheronolactone測定值之影響 72 圖 2-7 以 HPLC-UV 定量加酸處理 alpha-CEHC sulfate 標準品溶液樣品之 alpha-tocopheronolactone 層析圖譜74 圖2-8 HCl添加劑量 (A) 與 pH 值 (B) 對 alpha-CEHC 標準品溶液之 alpha-CEHC 與 alpha-tocopheronolactone測定值之影響75 圖 2-9 比較不同水解方式對鼠尿生成 alpha-CEHC 之影響78 圖 3-1 肝臟過氧化體 ACO1 酵素活性測定之原理103 圖3-2 維生素 E 與降血脂藥物 clofibrate 對大鼠肝臟過氧化體 ACO1 及微粒體 CYP4A1蛋白質表現量之影響135 圖 3-3 維生素 E 與降血脂藥物 clofibrate 對大鼠對大鼠肝臟CYP4A1, ACO1 及 D-BF mRNA 表現量之影響136 圖3-4不同劑量 clofibrate 處理後對大鼠肝臟 CYP4A1, ACO1/2, L-BF 及 D-BF mRNA 表現量之影響137 圖 3-5 不同劑量 clofibrate 處理後對大鼠尿液 alpha-CEHC 排出量與clofibrate 處理劑量、肝臟 CYP450 總量ACO1 活性之相關性分析141 圖 3-6 不同劑量 clofibrate 處理七天後對大鼠尿液 alpha-CEHC 排出量與肝臟 CYP4A1, ACO1/2, L-BF 及 D-BF mRNA表現量之相關性分析142 圖4-1 PFDA 之化學結構151 圖4-2 不同劑量 PFDA 處理對大鼠每日尿液 alpha-CEHC 排出量之影響170 圖4-3 各組大鼠從適應期至處理期之尿液 alpha-CEHC 變化量171 圖4-4 PFDA 處理對大鼠血清、肝臟 alpha-CEHC 含量及第七天尿液 alpha-CEHC 排出量之相關性分析172 圖4-5 不同劑量 PFDA 處理對大鼠肝臟 ACO1, CYP4A1, CYP3A1/2蛋白質表現量之影響177 圖4-6 不同劑量 PFDA 處理對大鼠肝臟 PPARalpha, CYP4A1, ACO1/2/3, PXR, CYP3A, CYP4F 及SULT mRNA 表現量之影響180 圖4-7 PFDA 處理對大鼠尿液 alpha-CEHC 排出量與肝臟 CYP450 總量、ACO 活性及 ACO1, CYP4A1, CYP3A1/2 蛋白質表現量之相關性分析183 圖5-1 維生素 E 代謝生成 alpha-CEHC 之可能路徑195 表 1-1 探討維生素 E 代謝途徑之相關文獻15 表 1-2 CEHCs 分析偵測方法之文獻統整.21 表 1-3 CYPs 的誘發受到不同核受器的調節35 表 2-1 alpha-CEHC、alpha-CEHC sulfate 標準品與鼠尿中 alpha-CEHC sulfate 之13C與 1H NMR 光譜之比較64 表 2-2 HCl添加劑量對大鼠尿液之 alpha-CEHC 與 alpha-tocopheronolactone測定值之影響71 表 2-3 HCl添加劑量對 alpha-CEHC sulfate 標準品溶液之 alpha-CEHC 與 alpha-tocopheronolactone測定值之影響73 表 2-4 HCl添加劑量對 alpha-CEHC標準品溶液之 alpha-CEHC 與 alpha-tocopheronolactone測定值之影響76 表 2-5 不同水解方式對 alpha-CEHC sulfate溶液生成 alpha-CEHC 與 alpha-tocopheronolactone 之影響77 表 2-6 鼠尿與 alpha-CEHC sulfate標準品溶液不同酸水解方式之 alpha-CEHC 回收率試驗79 表2-7 以不同水解方式處理鼠尿或人尿之 alpha-CEHC 定量結果81 表3-1 實驗一之試驗飼料組成91 表3-2 實驗二之試驗飼料組成92 表3-3 維生素 E 與降血脂藥物 clofibrate 對大鼠體重增加、攝食量及飼料利用效率之影響117 表3-4 維生素 E 與降血脂藥物 clofibrate 對大鼠各組織相對重量之影響118 表3-5維生素 E 與降血脂藥物 clofibrate 對大鼠血清及肝臟中三酸甘油酯及膽固醇含量之影響122 表3-6 維生素 E 與降血脂藥物 clofibrate 對大鼠血清及肝臟中 alpha-tocopherol 含量影響123 表3-7 維生素 E 與降血脂藥物 clofibrate 對大鼠飲水量、排尿量及尿液肌酸酐含量之影響127 表3-8 維生素 E 與降血脂藥物 clofibrate 對大鼠尿液中 alpha-CEHC含量之影響128 表3-9 維生素 E 與降血脂藥物 clofibrate 對大鼠維生素 E 攝入量對尿液中 alpha-CEHC排出量之影響 129 表3-10 維生素 E 與降血脂藥物 clofibrate 對大鼠肝臟微粒體中CYP450含量之影響131 表3-11 維生素 E 與降血脂藥物 clofibrate 對大鼠肝臟過氧化體 ACO1 活性之影響132 表3-12 維生素 E 與降血脂藥物 clofibrate 對大鼠尿液中 alpha-CEHC排出量與其維生素 E 攝入量、肝臟及血清 alpha-tocopherol 含量之相關性分析139 表3-13 維生素 E 與降血脂藥物 clofibrate 對大鼠尿液中 alpha-CEHC排出量與肝臟 CYP450 總量、ACO1 活性及 CYP4A1 蛋白質含量之相關性分析140 表4-1試驗飼料組成 153 表4-2 不同劑量 PFDA 處理對大鼠體重增加、攝食量及飼料利用效率之影響160 表4-3 不同劑量 PFDA 處理對大鼠各組織相對重量之影響 161 表4-4 不同劑量 PFDA 處理對大鼠血清及肝臟中三酸甘油酯及膽固醇含量之影響163 表4-5 不同劑量 PFDA 處理對大鼠血清、肝臟及脂肪組織 alpha-tocopherol 含量之影響165 表4-6 不同劑量 PFDA 處理對大鼠維生素 E 攝取量、喝水量、排尿量及尿液 alpha-CEHC含量之影響之影響 168 表4-7 不同劑量PFDA 處理對大鼠血清及肝臟 alpha-CEHC含量之影響 169 表4-8 不同劑量 PFDA 處理對大鼠肝臟微粒體中CYP450含量之影響175 表4-9 不同劑量PFDA 處理對大鼠肝臟過氧化體 ACO1 活性之影響 176 表4-10 PFDA 處理對大鼠尿液中 alpha-CEHC排出量與肝臟PPARalpha, ACO1/2/3, CYP4A1, PXR, CYP3A, CYP4F及SULT mRNA含量之相關性分析182 表5-1 Clofibrate 及 PFDA 對維生素 E 代謝生成 alpha-CEHC 之影響總整理 192 | |
dc.language.iso | zh-TW | |
dc.title | 鼠尿 alpha-CEHC Sulfate 純化鑑定與 Conjugated alpha-CEHC 分析方法之重建及活化 PPAR alpha 傳訊途徑對維生素 E 代謝生成 alpha-CEHC 之影響 | zh_TW |
dc.title | Isolation and Identification of alpha-CEHC Sulfate in Rat Urine and an Improved Method for the Determination of Conjugated alpha-CEHC and Effects of PPAR alpha Activation on the Metabolism of Vitamin E to alpha-CEHC | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 郭悅雄,胡淼琳,陳暉雯,劉珍芳,林璧鳳,蕭慧美 | |
dc.subject.keyword | 維生素 E 代謝,alpha-tocopherol,alpha-CEHC,alpha-CEHC sulfate,PPAR alpha,HPLC-ECD, | zh_TW |
dc.subject.keyword | vitamin E metabolism,alpha-tocopherol,alpha-CEHC,alpha-CEHC sulfate,PPAR alpha,HPLC-ECD, | en |
dc.relation.page | 219 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2009-06-26 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 微生物與生化學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
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