氧化壓力檢測平台之開發與降低血液透析病人氧化壓力之策略

The development of platform for measurement of oxidative stress and strategy for the decrease of oxidative stress in uremic patients with hemodialysis

陳冬生(Tung-Sheng Chen)

指導教授 ： 張炎林

中原大學/工學院/醫學工程研究所/博士(2009年)

https://doi.org/10.6840/cycu200900693

摘要

腎衰竭病人由於腎臟失去功能，導致代謝廢棄物無法藉由腎臟排出體外而累積在體內，這些累積在體內的代謝性廢物統稱為尿毒素，所以腎衰竭病人又稱尿毒症病人。血液透析治療最主要的目的是代替病人失去功能的腎臟藉由人工腎臟以濃度擴散(diffusion)及對流(convection)原理來移除血中多餘的水份及尿毒素。根據相關文獻指出，血液透析過程中，除了可以移除血中尿毒素之外，另外亦會因生物不相容性以及具有抗氧化性質的小分子之流失而造成病人體內氧化壓力上升。因此，給予血液透析病人服用抗氧化劑來提高病人體內抗氧化防禦機制便顯得非常重要。本實驗目的為開發「氧化-抗氧化檢測平台」，藉由此平台來篩檢血液透析病人體內氧化壓力值之大小和市售植物萃取物其抗氧化能力之高低。由實驗結果可知，以此平台在在評估混合型綠茶萃取物(green tea extract, GTE)、單一型綠茶萃取物(epigallocatechingallate, EGCG)、印度鵝莓(Indian gooseberry ,AMLA)、薔薇紅景天萃取物 (rhodiola rosea, RR)及薑黃素(curcumin , Cur)等五種市售萃取物，發現EGCG、AMLA及Cur以1:1:2.5的比例混合時，可以展現出最佳之抗氧化活性及最低之促氧化毒性。而以此抗氧化組合物給予13位患有糖尿病腎病變之血液透析病人服用三個月，發現其血液之總抗氧化能力(ferric reducing antioxidant power, FRAP)、血中氧化代謝產物指標(TBARS和peroxides)、糖尿病指標(glucose)及動脈硬化指標(LDL/HDL ratio、HDL)等皆比服用前有顯著的改善(p<0.05)。除此之外，追蹤服用此抗氧化組成物三個月後，病人其肝、腎功能及血液血球檢測均正常，顯示此抗氧化組合物具有改善體內氧化壓力及其相關併發症的潛力之外，亦無安全上的顧慮。冀望能以此研究所開發出來的檢測平台及抗氧化組合物，能輔佐降低血液透析病人血中氧化壓力及其相關併發症的發生率，藉以改善血液透析之品質，以增進病人的生活舒適度。

關鍵字

抗氧化物 ； 腎衰竭 ； 氧化壓力 ； 血液透析

並列摘要

The metabolic wastes accumulate in the patients with end stage renal failure due to the loss of renal function, and the metabolic wastes accumulating in the blood are called uremic solutes. The main purpose of hemodialysis is to replace dysfunctional kidney to remove uremic solutes through diffusion and convection. According to previous studies, the hemodialysis process induces the production of bioincompatibility and the reduction of small dialyzable solutes (including small uremic and antioxidant solutes). This is capable of initiating the increase of oxidative stress in dialysis patients. Thus, supplementation of antioxidants is important to increase antioxidant defense for dialysis patients. The aim of this study is to develop a platform for measurement of antioxidant-prooxidant properties for dialysis patients and commercial herbal extracts. Five commercial herbal extracts including green tea extract (GTE), epigallocatechin gallate (EGCG), Indian gooseberry (AMLA), rhodiola rosea (RR) and curcumin (Cur) were investigated by this platform. We found that the composition of EGCG, AMLA and Cur in the ratio of 1:1:2.5 showed the optimal antioxidant and prooxidant properties. Further, we observed that plasma antioxidant power (FRAP), oxidative stress (TBARS and peroxides), diabetic marker (plasma glucose) and atherogenic indices (LDL/HDL ratio, HDL) were significantly improved in 13 dialysis patients treated with the above antioxidant composition for three months (p<0.05). In addition, supplementation of the antioxidant composition did not influence blood cells, renal and liver functions for the experimental subjects. As shown in results, the antioxidant composition exhibits the potential in safety and improvement of oxidative stress in dialysis patients. We suggest that supplementation of antioxidant composition not only reduces the risk of complications associated with oxidative stress but also improves the quality of life for dialysis patients.

並列關鍵字

antioxidant ； renal failure ； oxidative stress ； hemodialysis

參考文獻

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