臺灣博碩士論文加值系統

摘 要
研究指出慢性腎衰竭患者隨著血液透析或連續式攜帶型腹膜透析的治療，會造成氧化壓力的增加。而目前對於給予血液透析患者口服抗氧化補充劑對抗氧化系統整體影響與時間效應並不十分清楚。因此本研究的目的主要是評估血液透析患者的飲食攝取與健康受試者是否有差異，及探討維生素C或/與E的口服補充對血液透析患者抗氧化防禦系統的影響，及追蹤在停止維生素C或/與E的補充後，血液透析患者體內的抗氧化能力。本研究以臺北醫學大學附設醫院血液透析中心門診常規血液透析病患為對象，經過篩選後，將38位患者平均分為四組：安慰劑 (400 mg 澱粉/次) 組、維生素C ( 400 mg L- ascorbic acid /次) 組、維生素E (400 mg d,l-α-tocopheryl acetate/次)組、維生素C ( 400 mg L- ascorbic acid/次) + 維生素E (400 mg d,l-α-tocopheryl acetate/次) 組，為期六週。於每次血液透析結束後，直接給予患者口服安慰劑或抗氧化補充劑共三顆膠囊，每週三次，血液透析患者於補充前(第零週)、補充期間(第三週)、補充後(第六週)、追蹤期間(第七、八週)與追蹤後(第十週)，在血液透析前、後各抽血分析。另以年齡分布與性別比例相似之健康受試者36人做為對照組。本實驗結果顯示：血液透析患者其飲食攝取與健康受試者無統計上的差異，且血液透析患者之飲食攝取量，並不受補充劑種類或補充時間的影響，表抗氧化效果的差異，由抗氧化維生素補充所造成。血液透析患者血漿中維生素C含量顯著低於健康受試者，透析後較透析前顯著下降達24%，表透析過程中維生素C會大量流失，給予抗氧化補充劑三週後於維生素C與C + E組較補充前顯著提昇；血漿中維生素E含量與健康受試者無差異，給予抗氧化補充劑六週後，於維生素E與維生素C + E組較補充前顯著提昇；另患者紅血球中麩胱甘的含量顯著的低於健康受試者，血液透析後與透析前並無統計差異，給予抗氧化補充劑六星期後皆較安慰劑組與補充前顯著的提昇。血漿總抗氧化狀態在血液透析前比正常值低者佔29%，血液透析後比正常值低者佔100%。顯示血液透析四小時治療過程中，會造成體內氧化壓力的增加，降低體內總抗氧化狀態；就組間效果上而言，補充三週後血漿總抗氧化狀態在維生素C + E組顯著大於維生素C組，與維生素E組則無差異；血液透析患者血漿中脂質過氧化物(malondialdehyde; MDA + 4-hydroxy-2(E)-nonenal; 4-HNE)的濃度顯著高於健康受試者，於血液透析前與透析後相比則無顯著差異；給予抗氧化補充劑六週後血漿中脂質過氧化物濃度皆較補充前顯著下降。總而言之，接受血液透析治療患者口服補充抗氧化維生素C或/與E六星期，可提高體內抗氧化狀態，減少脂質過氧化物的產生。
關鍵詞：維生素C、維生素E、抗氧化狀態、脂質過氧化、血液透析

Abstract
It has been reported that chronic renal failure patients with hemo- or continuous ambulatory peritoneal dialysis increase oxidative stress. However, it was not clearly known that the effects of oral antioxidant supplement on the overall antioxidant system and time course study in hemodialysis patients. This study was to evaluate if dietary intake was different between hemodialysis patients and healthy subjects, and to investigate the supplementation with vitamin C or/and E on antioxidant capacity in hemodialysis patients. The patients routinely receiving hemodialysis were recruited from the center of hemodialysis at Taipei Medical University Hospital. After screening, thirty-eight patients were divided into four groups: placebo (400 mg starch/time), vitamin C- (400 mg/time), vitamin E- (400 mg d,l-a-tocopheryl acetate/time), and vitamin C (400 mg/time) + E (400 mg d,l-a-tocopheryl acetate/time)-supplemented groups for 6 weeks. The patients orally received three capsules three times a week right after finishing hemodialysis. Blood samples from pre- and post-dialysis were drawn before (week 0), during (week 3), and after (week 6) supplementation, as well as during (week 7, 8) and after (week 10) follow-up. Additionally, thirty-six healthy subjects with similar age and sex distribution were selected as the control group. The results showed that dietary intake was not significantly different between hemodialysis patients and healthy subjects. Both antioxidant supplements and supplemented duration did not affect dietary intake of hemodialysis patients, indicating the difference of antioxidant capacity resulted from antioxidant supplements. Plasma vitamin C concentration was significantly decreased in hemodialysis patients compared with healthy subjects, and significantly lowered by 24% from post-dialysis compared with pre-dialysis, suggesting vitamin C was greatly lost during hemodialysis. After 3-week antioxidant supplementation, vitamin C- and vitamin C + E-supplemented groups significantly elevated plasma vitamin C levels compared with those at the baseline. Hemodialysis patients had similar plasma vitamin E concentration as healthy subjects. Plasma vitamin E concentrations were significantly higher in vitamin E- and vitamin C + E-supplemented groups at week 6 than those at week 0. Erythrocyte glutathione levels were also lower in hemodialysis patients than in healthy subjects, but were not significantly different between post- and pre-dialysis. All antioxidant supplements elevated erythrocyte glutathione at week 6 compared with placebo group and the baseline. Total antioxidant status was lower than the normal range in 29% hemodialysis patients from pre-dialysis, and in 100% hemodialysis patients from post-dialysis, indicating increased oxidative stress and impaired total antioxidant status during 4-h hemodialysis. Vitamin C + E-supplemented group had higher total antioxidant status than vitamin C-supplemented group at week 3, but had similar level as vitamin E-supplemented group. Hemodialysis patients had greater plasma lipid peroxide (malondialdehyde; MDA + 4-hydroxy-2(E)-nonenal; 4-HNE) levels than healthy subjects, but no significant difference was found from post- and pre-dialysis. All antioxidant supplements decreased plasma lipid peroxides at week 6 compared with at the baseline. Therefore, oral supplementation with vitamin C or/and vitamin E for 6 weeks could improve antioxidant status and decrease lipid peroxide production in hemodialysis patients.
Key words: vitamin C, vitamin E, antioxidant status, lipid peroxidation, hemodialysis

目 錄
摘 要I
AbstractIII
致 謝V
目 錄VII
表目次IX
圖目次X
第一章 緒論1
第二章 文獻回顧3
第一節 台灣地區透析患者流行病學調查資料6
第二節 血液透析患者之營養狀況7
第三節 血液透析患者體內氧化與抗氧化防禦系統狀況12
第四節 血液透析患者血脂質狀況20
第五節 造成慢性腎衰竭血液透析患者罹患心血管疾病的可能因子24
第六節 抗氧化維生素C與維生素E簡介29
第三章 實驗設計與方法33
第一節 受試者標準與數目33
第二節 研究期間可能傷害與處理方式34
第三節 飲食攝取評估35
第四節 抗氧化維生素的補充37
第五節 血液收集40
第六節 血漿中維生素C濃度之測定42
第七節 血漿中維生素E濃度之測定43
第八節 紅血球中麩胱甘濃度之測定45
第九節 血漿中總抗氧化狀態之測定46
第十節 血漿中脂質過氧化物濃度之測定48
第十一節 統計分析49
第四章 結 果50
第一節 受試者基本資料50
第二節 研究期間受試者飲食攝取狀況53
第三節 血液透析患者補充抗氧化維生素前、後血漿中維生素C含量55
第四節 血液透析患者補充抗氧化維生素前、後血漿中維生素E含量60
第五節 血液透析患者補充抗氧化維生素前、後紅血球中還原型麩胱甘含量65
第六節 血液透析患者補充抗氧化維生素前、後血漿中總抗氧化狀態70
第七節 血液透析患者補充抗氧化維生素前、後血漿中脂質過氧化物含量75
第五章 討論81
第一節 受試者基本資料與飲食攝取狀況分析81
第二節 抗氧化營養素補充劑量安全性的探討84
第三節 血液透析患者補充抗氧化維生素前、後血漿中維生素C含量分析87
第四節 血液透析患者補充抗氧化維生素前、後血漿中維生素E含量分析89
第五節 血液透析患者補充抗氧化維生素前、後紅血球中還原型麩胱含量分析89
第六節 血液透析患者補充抗氧化維生素前、後血漿中總抗氧化狀態分析91
第七節 血液透析患者補充抗氧化維生素前、後血漿中脂質過氧化物含量分析92
第六章 結論94
第七章 參考文獻96
附錄105
附錄 A 血液透析患者篩選基本問卷105
附錄 B 健康受試者篩選基本問卷107
附錄 C 血液透析患者參與計畫志願書108
附錄 D 健康受試者參與計畫同意書110
附錄 E 計畫進行通知與配合說明111
附錄 F 給予血液透析患者抽血與補充劑之流程113
附錄 G 二十四小時飲食回憶紀錄標準法與範本114
附錄 H 二十四小時飲食回憶紀錄表122
表目次
表 一、尿毒症狀在身體各系統的表現5
表 二、評估血液透析患者營養狀況的指標8
表 三、造成血液透析患者營養不良的因子9
表 四、含氧自由基種類及其半衰期15
表 五、氧自由基對生物體分子的傷害與可能導致的病變16
表 六、透析患者高脂血症的特徵22
表 七、動脈粥狀硬化生成的危險因子28
表 八、健康受試者與四組血液透析患者補充前之臨床基本資料52
表 九、以二十四小時飲食回憶法評估健康受試者與血液透析患者於研究期間之飲食攝取量54
表 十、健康受試者與血液透析患者補充抗氧化維生素前、後血漿中維生素C於透析前之含量58
表 十一、血液透析患者補充抗氧化維生素前、後血漿中維生素C於透析前、後之含量59
表 十二、健康受試者與血液透析患者補充抗氧化維生素前、後血漿中維生素E於透析前之含量63
表 十三、血液透析患者補充抗氧化維生素前、後血漿中維生素E於透析前、後之含量64
表 十四、健康受試者與血液透析患者補充抗氧化維生素前、後紅血球中還原型麩胱甘於透析前之含量68
表 十五、血液透析患者補充抗氧化維生素前、後紅血球中還原型麩胱甘於透析前、後之含量69
表 十六、健康受試者與血液透析患者補充抗氧化維生素前、後血漿中於透析前之總抗氧化狀態73
表 十七、血液透析患者補充抗氧化維生素前、後血漿中總抗氧化狀態於透析前、後之含量74
表 十八、健康受試者與血液透析患者補充抗氧化維生素前、後血漿中脂質過氧化物於透析前之濃度77
表 十九、血液透析患者補充抗氧化維生素前、後血漿中脂質過氧化物於透析前、後之含量78
表 二十、血液透析患者於補充後期第六週血中各分析項目與補充前第零週之比較79
表 二十一、血液透析患者於追蹤後期第十週血中各分析項目與補充後期第六週之比較80
圖目次
圖 一、脂質過氧化反應機制23
圖 二、二十四小時飲食回憶法資料收集與處理流程圖36
圖 三、安慰劑與抗氧化補充劑的膠囊型式39
圖 四、實驗流程圖41

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