慢性阻塞性肺疾病(COPD)是一種慢性氣道阻塞的病症。根據文獻報告，下呼吸道氧化物與抗氧化物失衡可能是導致COPD的主因，由發炎細胞和抽菸所產生的氧化物，可能會造成細支氣管緊縮、纖維化、變窄，並直接傷害肺泡壁，降低肺功能。本研究的目的在探討補充抗氧化維生素C或/和E後對慢性阻塞性肺疾病患者體內抗氧化狀況的影響。受試者為42個男性的慢性阻塞性肺疾病門診患者，以一秒量(FEV1) < 70%及一秒率(FEV1/FVC) < 75%為收案的依據。實驗採隨機平行、雙盲試驗方式進行，將其分為四組，分別補充安慰劑、維生素E (400 IU/day)、維生素C (500 mg/day)、及維生素C+E，為期13週。研究結果如下：補充抗氧化維生素C及C＋E會顯著的降低血漿中總膽固醇的濃度(p < 0.05)，補充維生素C可顯著的降低血漿中高密度脂蛋白膽固醇及脂質過氧化物isoprostanes的濃度(p < 0.05)。除此之外，補充抗氧化維生素後有以下的趨勢：即補充維生素E及C＋E後有降低超氧化物岐化酉每 (SOD)活性的情形，補充維生素C或/和E後有降低麩胱甘月太 過氧化酉每 (GSH-Px)的活性、降低脂質過氧化物丙二醛(MDA)的值、延長低密度脂蛋白氧化延遲時間和增加總捕捉自由基能力的趨勢。本研究已顯現補充抗氧化維生素後對COPD患者抗氧化狀況的正面改善趨勢，所以很值得以本研究為基礎，做再更深入的研究，探討其相關性，將有利於此疾病的防患與治療。

Chronic obstructive pulmonary disease (COPD) is an obstructive airway disorder. An imbalance between oxidants and antioxidants has been proposed in the pathogenesis of COPD. No matter the source of oxidant, such as the inhaled from smoking or generated from leucocytes, it not only makes bronchiolar constriction, fibrosis, and narrowing, but also hurt lung cell wall and decline lung function. The aim of the study was to investigate the effect of antioxidant vitamin C & E supplement on the antioxidative status in COPD patients. Forty-two male COPD outpatients were double-blinded, randomly divided into four groups supplement with placebo or vitamin E (400 IU/day) or vitamin C (500 mg/day) or vitamin C+E daily for 13 weeks. The antioxidative status of COPD patients was evaluated. Results showed after supplementation with vitamin C and C+E significantly lowering plasma total cholesterol concentration (p < 0.05). Supplementation with vitamin C result in statistically significantly lowering high density lipoprotein cholesterol and attenuation of plasma isoprostanes -- the product of lipid peroxidation (p < 0.05). More than these, patients had the trend to reduce antioxidative enzymes activity and plasma malondialdehyde, to prolong the lag-time of LDL oxidation and to increase total radical trapping antioxidant parameter after 13-week supplementation. Therefore, supplement with antioxidant vitamins may play a role in reduce the oxidative stress of COPD patients.

目 錄
中文摘要……………………………………………………………….I
英文摘要……………………………………………………………….Ⅱ
縮寫對照表……………………………………………………………….Ⅲ
致謝…………………………………………………………………....Ⅳ
目錄……………………………………………………………………...Ⅶ
表目次…………………………………………………………………….ⅩI
圖目次…………………………………………………………………….ⅩⅡ
第一章緒論……………………..……………………………..………..….. 1
第二章文獻回顧……………………………….…………....………...….... 3
第一節慢性阻塞性肺疾病………………………………………….… 3
壹疾病定義………………...…………………………………….. 3
貳肺功能檢查…………...……………………………………….. 3
第二節氧化壓力對慢性阻塞性肺疾病的影響………………………. 4
壹自由基的定義………………………...…………………..…… 4
貳自由基的來源……………………………...………………..… 5
參自由基與慢性阻塞性肺疾病的關係………………….....…… 7
肆氧化壓力的指標…………………………………………..….. 10
第三節身體的抗氧化防禦系統………………………...………….... 12
壹抗氧化防禦系統…...……………………………………..….. 12
貳維生素E及維生素C的作用機轉……………………..…….13
第四節抽煙對抗氧化物的影響…………………………………...… 16
第五節抗氧化維生素與慢性阻塞性肺疾病的關係………….…….. 16
第六節抗氧化維生素對肺功能的影響………………….………….. 17
第三章實驗設計與材料方法…………………………………………….. 20
第一節維生素C & E的製備…………………………………..……. 20
第二節受試者招募及篩選…….……………………………….……. 20
第三節實驗設計……………….……………………………….……. 21
第四節實驗過程……………….…………………………………...... 23
第五節身高、體重及體脂肪測量………….……………………….. 24
第六節肺功能測定法…………….……………………………...…... 24
第七節飲食評估……….…………………………………….…....…. 25
第八節血液處理….………………………………………...……..…. 25
第九節低密度脂蛋白之氧化延遲時間測試………….…..……...…. 27
壹超高速離心分離低密度脂蛋白...……………………….…... 27
貳低密度脂蛋白之透析……………..…………………………. 27
參LDL中蛋白質測定………………..………………….…….... 28
肆低密度脂蛋白氧化延遲時間(lag time)測量………….....….. 28
第十節血漿中脂質過氧化物濃度的測定……….………….………..30
壹血漿中Thiobarbituric acid-reactive substances之濃度測試....30
貳血漿中Isoprostane之濃度測試…...……………..………….. 31
第十一節血球中抗氧化酵素活性之測定………………………….. 34
壹麩胱甘月太過氧化酉每活性之測定...………...………..…….…. 34
貳超氧化物岐化酉每之活性之測定………...…...…………..….. 35
第十二節血漿中抗氧化物質之測定……………………………...... 37
壹硫氫基化合物…………...….…………………………...…… 37
貳維生素C……………..……………...……...…………………38
參維生素E…………...………………...………………………. 40
肆捕捉自由基的抗氧化能力的計算…………...……….……... 41
第十三節統計分析…………………………………………………...42
第四章結果……………………………………………………………….. 43
第一節受試者的基本資料分析……………...…………………….... 43
第二節受試者補充抗氧化維生素前後之飲食攝取情形…………... 45
第三節受試者補充抗氧化維生素前後之肺功能檢查及變化情形... 49
第四節受試者補充抗氧化維生素前後之體位測量值及變化情形.. 52
第五節受試者補充抗氧化維生素前後之血液生化值及變化情形.. 55
第六節受試者補充抗氧化維生素前後之血脂質含量及變化情形.. 58
第七節受試者補充抗氧化維生素前後之血中抗氧化酵素活性及
變化情形……………………………………………………... 61
壹補充抗氧化維生素對超氧化物岐化酉每 活性的影響…...…. 61
貳補充抗氧化維生素對麩胱甘月太 過氧化酉每 活性的影響…... 61
第八節受試者補充抗氧化維生素前後之脂質過氧化產物及變化
情形…………………………………………………………... 66
壹補充抗氧化維生素對TBARs的影響….………………..… 66
貳補充抗氧化維生素對血漿中isoprostane的影響…..……... 69
第九節受試者補充抗氧化維生素前後之低密度脂蛋白氧化延遲
時間及變化情形.…………………………………………….. 71
第十節受試者補充抗氧化維生素前後之抗氧化物質及變化情形... 73
第十一節受試者補充抗氧化維生素後各種測量值變化量的相關
性分析………………………………………………...……… 76
第五章討論……………………………………………………………….. 78
第一節受試者基本資料……………………………………………... 78
第二節受試者飲食攝取探討………………………………………... 78
第三節膳食中的維生素C及E對肺功能的影響……….………….. 81
第四節受試者體位測量值…………………………………………... 82
第五節受試者血液生化值…………………………………………... 83
第六節補充抗氧化維生素對血脂質的影響………………………... 83
壹補充抗氧化維生素C及C＋E後會降低總膽固醇的濃度… 83
貳補充抗氧化維生素C後會降低高密度脂蛋白膽固醇的
濃度…………………………………………….……..…...…. 84
第七節補充抗氧化維生素會影響血中抗氧化酵素的活性.……...... 85
壹補充抗氧化維生素E及C＋E後有降低SOD活性的趨勢.…... 85
貳補充抗氧化維生素C或/和E有降低GSH-Px活性的趨勢.. 86
第八節補充抗氧化維生素可以降低脂質過氧化產物...………….....87
壹補充抗氧化維生素後有降低血漿TBARs值的趨勢…..…… 87
貳補充抗氧化維生素C後可以明顯的降低脂質過氧化物isoprostanes的值…………………………….…………...…... 88
第九節補充抗氧化維生素具有延長低密度脂蛋白氧化延遲時間
的趨勢……………………………………………………...… 89
第十節補充抗氧化維生素具有提升總捕捉自由基能力的趨勢…... 90
第六章總論……………………………………….………………..….….. 92
第一節結論……………………………………………………….…. 92
第二節建議……………………………………………………….…. 93
參考文獻…………………………………………………………..…….…. 94
附錄…………………………………………………………………….…. 103
A 基本資料問卷………………………………………...…...….…... 103
B 二十四小時飲食回憶問卷……………………………….…….… 105表目次
.頁數
表一 受試者基本資料分析…………………….……………………….. 44
表二 受試者抽菸情形………………………….……………………….. 44
表三 受試者於實驗期間飲食攝取情形……….…………………….…. 46
表四 受試者補充抗氧化維生素前後之飲食攝取情形…….….………. 47
表五 受試者補充抗氧化維生素前後之飲食攝取變化情形….…….…. 48
表六 受試者補充抗氧化維生素前後之肺功能檢查…………..………. 50
表七 受試者補充抗氧化維生素前後之肺功能檢查及變化情形….….. 51
表八 受試者補充抗氧化維生素前後之體位測量值…………….….…. 53
表九 受試者補充抗氧化維生素前後之體位測量變化值…………...… 54
表十 受試者補充抗氧化維生素前後之血液生化值含量…….…….…. 56
表十一 受試者補充抗氧化維生素前後之血液生化值變化量.…….…. 57
表十二 受試者補充抗氧化維生素前後之血脂質含量……….….……. 59
表十三 受試者補充抗氧化維生素前後之血脂質變化情形……..……. 60
表十四 受試者補充抗氧化維生素前後之血中SOD變化情形…..…... 63
表十五 受試者補充抗氧化維生素前後血中GSH-Px變化情形…..….. 64
表十六 血液中抗氧化酵素的多變量分析……………………………... 65
表十七 受試者補充維生素前後之脂質過氧化產物變化情形…..……. 67
表十八 TBARs的多變量分析……………………………………….…. 68
表十九 受試者補充維生素前後之脂質過氧化產物變化情形…..……. 70
表二十 受試者補充維生素前後LDL氧化延遲時間變化情形……….. 72
表二十一 受試者補充抗氧化維生素前後之抗氧化物質含量……...….. 74
表二十二 受試者補充抗氧化維生素前後之抗氧化物質變化情形……. 75
表二十三 補充抗氧化維生素後各種測量值變化量的相關性分析…..... 77
圖目次
頁數
圖一 香菸中的成分………………………..……………………………... 6
圖二 抽菸、氧化壓力和慢性阻塞性肺疾病的關係……………………. 9
圖三 Isoprostanes的生成路徑……………………………………..……. 12
圖四 維生素E的結構及其氧化產物…………………………..………. 14
圖五 維生素C的結構及其氧化和分解產物………………………..…. 15
圖六 實驗流程圖…………………………………………….……….….. 22
圖七 LDL氧化延遲時間之動力曲線……………………….……….….. 29

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