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研究生: 黃秋薇
Chiu-Wei Huang
論文名稱: Isoflavones對賀爾蒙補充治療之停經婦女血脂與脂蛋白及尿液雌激素代謝物的影響
The effect of supplementation with isoflavones on plasma lipids, lipoproteins and urinary estrogen metabolites in postmenopausalwomen with hormone replacement therapy
指導教授: 吳文惠
Wu, Wen-Huey
學位類別: 碩士
Master
系所名稱: 人類發展與家庭學系
Department of Human Development and Family Studies
論文出版年: 2000
畢業學年度: 88
語文別: 中文
中文關鍵詞: isoflavones、賀爾蒙補充治療、三酸甘油酯、膽固醇、LDL氧化性、2OHE1、16αOHE1
英文關鍵詞: isoflavone, HRT(Hormone replacement therapy), 2OHE1,16αOHE1, LDL oxidation .
論文種類: 學術論文
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  • 本研究目的主要探討isoflavones的攝取對於有接受賀爾蒙補充治療之停經後婦女血脂、尿液中雌激素代謝物2-hydroxyestrone (2OHE1)、16α-hydroxyestrone(16αOHE1)濃度及其比值2OHE1 /16αOHE1(乳癌生化指標)與抗氧化性的影響,以期了解isoflavones在保護心血管疾病與抗癌上的效果。
    自醫院募集停經一年以上、身體健康且無服用isoflavones相關產品之停經婦女35名,受試者需接受賀爾蒙治療至少3個月以上,且方式為每天服用premarin 0.625毫克及provera 5毫克。實驗設計為單盲比較試驗,實驗前先給予每天6克的麥芽糊精作為安慰劑共14天,之後改服用純化自黃豆胚軸的isoflavones製劑,每天6克(約可攝取到114毫克isoflavones)共28天。實驗前後各採集一次空腹血液及早晨起床後第一次尿液,分析血漿及各種脂蛋白中的三酸甘油酯、膽固醇含量、血漿中總抗氧化狀態、isoflavones濃度、LDL氧化遲滯期和TBARS產生量與尿液中isoprostane、2OHE1、16αOHE1等含量的測量。
    結果顯示服用isoflavones後血漿中daidzein濃度較基礎期明顯增加,然而血漿與各種脂蛋白中的膽固醇、三酸甘油酯並沒有顯著影響,但HDL-C濃度及LDL-C/ HDL-C比值則分別在服用isoflavones後顯著增加及減少。儘管血漿總抗氧化狀態與尿液中isoprostane濃度並無顯著差異但LDL體外氧化實驗則能夠延長氧化遲滯期並減少TBARS產生量。而尿液中雌激素代謝物分佈於服用isoflavones前後並無顯著差異。由本研究結果來看,isoflavones可上升HDL-C,進而下降LDL-C/ HDL-C比值,且能增加LDL體外氧化耐受性及下降TBARS產生量,對停經後婦女在心血管疾病的預防上或許是有助益的,但對尿液雌激素代謝物則無影響。

    Isoflavones are soy phytoestrogens that have been suggested to be cardioprotective and anticarcinogenic. The aims of this trial were to determine the effect of supplementation with isoflavones on plasma lipids, oxidisability of low density lipoprotein ex vivo and two major urinary estrogen metabolites ( as a biomarker for breast cancer risk ) in postmenopausal women with hormone replacement therapy. Thirty-five apparently healthy postmenopausal women having taken combined continuous hormone replacement therapy (premarin 0.625mg, provera 5mg) for at least 3 monthes participated in a single-blind trial. An initial 14-day placebo period of supplementation with maltodextrin was followed by 28 -day periods of supplementation with 114mg isoflavones per day . Venous blood and fist morning urine sample were collected initially and at the end of isoflavone supple-mentation. Supplementation resulted in a 5-fold increase in plasma daidzein concentration. No changes in the plasma concentrations of total cholesterol , triglyceride or total antioxidant status and the urinary excretion of isoprostane or the estrogen metabolites : 2-hydroxyestrone, 16α-hydroxyestrone were observed following supplementation. However an significant beneficial effect was noted for the concentration of HDL-C or LDL-C /HDL-C ratio and in the oxidisability of LDL.The results suggest that isoflavones ameliorate the cardiovascular risk in postmenopausal women, but no effect on urinary estrogen metabolism.

    中文摘要 Ⅰ 英文摘要 Ⅱ 第一章 前言 1 第二章 文獻探討 3 一、 Isoflavones的簡介 3 (一) Isoflavones的發現與化學結構 3 (二) Isoflavones的消化吸收與生物利用率 5 二、 Isoflavones的生理作用 10 (一) 賀爾蒙的影響 10 (二) 抗氧化作用 14 (三) 抑制血管增生 19 (四) 抑制腫瘤細胞增殖 20 三、 Isoflavones與停經婦女健康相關的研究 20 (一) 減緩停經症狀 21 (二) 預防骨質疏鬆症 22 (三) 預防乳癌 25 (四) 預防心血管疾病 28 第三章 材料與方法 33 一、 市售黃豆製品分析 33 二、 人體實驗對象 33 三、 實驗設計 35 四、 實驗器材 37 五、 實驗材料 38 六、 分析項目與方法 40 (一) 市售各種黃豆製品與實驗補充品 40 (二) 血液的收集 41 (三) 血漿的分離 42 (四) 尿液的收集 42 (五) 血漿總抗氧化狀態的測定 42 (六) 血漿中isoflavones的測定 43 (七) 脂蛋白的分離 44 (八) 膽固醇之測定 45 (九) 三酸甘油酯之測定 45 (十) 低密度脂蛋白的透析及其蛋白質濃度的測定46 (十一) 尿液creatinine測量 47 (十二) 尿液isoprostane含量測定 48 (十三) 尿液estrogen 代謝物2OHE1/16α2OHE1含量分析50 五、 實驗品質控制 53 六、 統計分析 54 七、 實驗限制 55 第四章 結果 56 一、 市售各種黃豆製品中異黃酮含量之分析 56 二、 市售黃酮製劑中異黃酮含量 56 三、 受試者募集 57 四、 受試者基本資料 57 五、 受試者問卷調查 58 六、 血中三酸甘油脂的變化 58 七、 血中膽固醇的變化 59 八、 血漿中抗氧化狀態及異黃酮濃度的改變 59 九、 TBARS產生及變化 59 十、 Conjugated diene 形成之 lag time及變化60 十一、 尿液中雌激素代謝分佈的情形 60 十二、 尿液中氧化物質Isoprostane濃度的變化 61 十三、 受試者服用異黃酮後血漿中HDL-C濃度變化量與daidzein濃度 變化量間的相關性 61 十四、 受試者服用異黃酮後血漿中LDL脂蛋白以銅離子催化氧化反應 時conjugated dienes形成之lag time 變化及TBARS變化量與 daidzein濃度變化量間的相關性 62 第五章 討論 79 一、 黃豆製品中異黃酮含量的分析 79 二、 血中異黃酮濃度的變化 80 三、 血中三酸甘油脂濃度的變化 81 四、 血漿中膽固醇的變化 81 五、 抗氧化性的改變 82 六、 尿液中雌激素代謝物分佈的變化 86 第六章 總結 88 參考文獻 90 附錄一 邀請停經婦女參加服用異黃酮之計畫 110 附錄二 問卷調查 113 附錄三 飲食調查問卷 115 附錄四 同意書 117 附錄五 收集尿液以及血液注意事項 118 附錄六 服用賀爾蒙及異黃酮紀錄表 119 表目錄 表一、 phytoestrogens與雌激素接受體親和 11 表二、 potential mechanisms for a beneficial effect of soy protein on decreasing cardiovascular diseaes risk 30 表三、 市售黃豆製品每100g產品中所含genistein及daidsein濃度 63 表四、 市售黃酮製劑中之Isoflavones含量 65 表五、 受試者基本料 66 表六、 受試者服用異黃酮前後血漿及各種脂蛋白中三酸甘油酯的濃度 67 表七、 受試者服用異黃酮前後血漿及各種脂蛋白中膽固醇含量 68 表八、 受試者服用異黃酮前後血漿中總抗氧化狀態與異黃酮濃度 69 表九、 受試者服用異黃酮前或後LDL以銅離子催化氧化反應時 conjugated dienes 形成之lag time與TBAR產生量及變化 70 表十、 不同批實驗測量受試者服用異黃酮前或後LDL以銅離子催化氧 化反應時TBARS產生量及變化 71 表十一、 受試者服用異黃酮前後尿液中賀爾蒙代謝物分佈與氧化物濃度 72 表十二、 受試者服用異黃酮前後血漿中高密度脂蛋白膽固醇含量、 Isoflavone含量及低密度脂蛋白與高密度脂蛋白比的變化 73 圖目錄 圖一、 genistein化學結構及在分解或代謝作用不同步驟的鍵結 4 圖二、 Isoflavones的代謝簡圖 6 圖三、 daidazin及genisiein被人類腸道細菌分解代謝途徑 7 圖四、 比較內生性(endogenous estrong)、植物性 (isoflavone,lignans)及合成雌激素(synthetic molecules)的化學結構 12 圖五、 Calibration curves of genistein,daidzen,butyrophenone 74 圖六、 受試者服用異黃酮前後血漿中異黃酮含量 75 圖七、 受試者服用異黃酮前後血漿及各種脂蛋白中膽固醇含量 76 圖八、 受試者服用異黃酮前後對低密度脂蛋白TBARS濃度的影響 77 圖九、 每位受試者服用異黃酮前後之LDL以銅離子催化氧化反應時 conjugated diene形成之lag time變化 78

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