臺灣博碩士論文加值系統

血液透析為目前最常採用治療末期腎臟疾病(ESRD)之療法，是以擴散及運流方式將血液中的尿毒溶質去除。本研究第一部份探討血液透析時使用之透析器血液廓清特性。血液廓清的部份是依照國際標準ISO8637:2010要求，測試國內研發的中空纖維透析器廓清率性能。透析器有兩型160及180，各取3個透析器進行測試。透析器廓清率性能測試範圍涵蓋廠商標示之血液流量、透析液流量以及溶質之總質傳面積係數(K0A)。測試溶質包括尿素、肌酸酐、磷酸鹽及維生素B12。在透析液流量為500 mL/min及血液流量為200、300、350、400及500 mL/min下計算之廓清率值，再經計算求得平均K0A，得到透析器160及180對於四種溶質之K0A為824、588、518、302 mL/min及894、642、549、316 mL/min。然而利用理論公式計算出不同流量下之廓清率理論值，其結果與實驗值相較之下偏差值在±5%內，顯示理論公式可用於臨床應用計算。第二部份是於透析液中添加鐵焦磷酸鹽及EGCG抗氧化劑，探討含鐵質及抗氧化透析液之潛在應用。結果顯示鐵質透析液會造成血液中脂質氧化程度上升。透析液中含EGCG在透析5分鐘後血液中測得FRAP數值逐漸上升，表示EGCG逐漸進入血液中，且在透析期間皆能穩定提供定量EGCG，能夠增加血液中的抗氧化能力並保護血液中成份避免鐵質對人體造成的氧化損傷，可以用來改善透析患者體內之氧化壓力。

Hemodialysis is the most comment method for the treatment of patients with end-stage renal failure (ESRD). The principle of hemodialysis is to remove uremic toxins from uremic patients through diffusion and convection. This dissertation includes two parts. First part of this dissertation is to discuss about the characteristics of clearance for hemodialyzers based on ISO regulation ISO8637:2010. The tested hemodialyzers were produced in Taiwan. The models of the tested hemodialyzers were 160 and 180. The results for all of the evaluations were obtained by performing 3 hemodialyzers for each model. The evaluations for hemodialyzers covered all necessary indices including blood flow, dialysate flow, K0A, and clearance of blood urea, creatinine, phosphorous ion as well as vitamin B12. Under constant dialysate flow rate (500 mL/min) and different blood flow rates (200, 300, 350, 400 and 500 mL/min), we found that mean K0A values for hemodialyzer model 160 and 180 are 824, 588, 518, 320 mL/min and 894, 624, 549, 316 mL/min, respectively based on the clearance of above dialysate solutes. In addition, we calculated the theoretical clearance values for above two hemodialyzers by using theoretical equations. The variable between theoretical clearance values and experimental clearance values is less than 5%. This result shows that the theoretical equations may be applied in clinical use in calculating clearance values for hemodialyzer. Second part of my dissertation is to discuss the potential use of ferric pyrophosphate and epigallocatechin gallate (EGCG) in dialysate. The experimental results showed that addition of ferric pyrophosphate into dialysate (iron dialysate) is capable of inducing the increase of oxidative stress during hemodialysis. Meanwhile, addition of ferric pyrophosphate and EGCG into dialysate (iron-EGCG dialysate) can reduce oxidative stress induced by iron. This result may be due to the diffusion of EGCG from dialysate to blood, leading to increase antioxidant potential of blood and decrease oxidative damage induced by iron. We suggest that these findings could be an effective method for improving oxidative stress in patients with hemodialysis.

摘要 I
Abstract II
致謝 IV
目錄 V
圖索引 VIII
表索引 IX

第一章 緒論 1
1.1 前言 1
1.2 研究目的 1
第二章 文獻回顧 2
2.1 腎臟與腎衰竭 2
2.1.1 腎臟移植 2
2.1.2 腹膜透析 2
2.1.3 血液透析 3
2.2 血液透析系統 5
2.2.1 透析液迴路 6
2.2.2 體外血液迴路 6
2.3 透析膜材質 7
2.3.1 天然纖維膜 7
2.3.2 半合成纖維膜 8
2.3.3 人工合成膜 9
2.4 廓清率(Clearance) 9
2.5 透析器性能 11
2.6 血液透析時可透析物質 12
2.7 含鐵質透析液 12
2.8 血液透析與氧化壓力 13
2.9 抗氧化劑的選擇 13
2.9.1 EGCG 15
2.10 鐵質與EGCG透析液 16
第三章 質傳理論 17
3.1 透析器之廓清率與總質傳面積係數 17
第四章 實驗材料與方法 20
4.1 實驗設備 20
4.2 實驗試劑 21
4.3 溶質廓清性能試驗 23
4.4 鐵質與EGCG透析液實驗 25
4.5 檢測原理及步驟 26
4.5.1 尿素(Urea) 26
4.5.2 肌酸酐(Creatinine) 28
4.5.3 無機磷酸鹽(Inorganic phosphate) 29
4.5.4 維生素B12(Vitamin B12) 30
4.5.5 總抗氧化能力(FRAP) 31
4.5.6 脂質氧化狀態(TBARS) 31
第五章 結果與討論 33
5.1 溶質廓清性能試驗 33
5.1.1 改變血液流量之特性 33
5.1.2 改變超過濾流量之特性 35
5.1.3 廓清率理論值與實驗值比較 36
5.1.4 改變透析液流量之特性 38
5.2 鐵質與EGCG透析液實驗 41
5.2.1 血液中總抗氧化能力 41
5.2.2 血液中脂質氧化狀態 42
第六章 結論 44
第七章 未來展望 45
符號說明 46
參考文獻 47

附錄 1 透析器160於QD=500 mL/min，不同血液流量下QF=0 mL/min增加為16.7 mL/min，廓清率增加百分比 54
附錄 2 透析器180於QD=500 mL/min，不同血液流量下QF=0 mL/min增加為16.7 mL/min，廓清率增加百分比 55
附錄 3 透析器160於QD=500 mL/min，QF=0 mL/min，不同血液流量之廓清率值、K0A值、K0A理論值與理論值及實驗值偏差百分比 56
附錄 4 透析器180於QD=500 mL/min，QF=0 mL/min，不同血液流量之廓清率值、K0A值、K0A理論值與理論值及實驗值偏差百分比 57
附錄 5 模擬透析抗氧化能力(FRAP)檢測數據 58
附錄 6 模擬透析脂質氧化狀態(TBARS)檢測數據 61

圖索引
圖- 1 簡易血液透析示意圖 3
圖- 2 血液透析溶質擴散示意圖 4
圖- 3 運流作用示意圖 5
圖- 4 血液透析系統示意圖 5
圖- 5 影響透析器性能參數A.血液流量及溶質分子與廓清率之關係 B.透析液流量及溶質分子與廓清率之關係 C.膜面積與尿素廓清率之關係 10
圖- 6 類黃酮基本結構 15
圖- 7 EGCG抗氧化機制 15
圖- 8 透析器從血液廓清至透析液物質傳送示意圖 17
圖- 9 透析器從透析液廓清至血液物質傳送示意圖 17
圖- 10 血液透析器測量廓清率之開放迴路系統圖 23
圖- 11 透析器160在QF=0 mL/min及QD=500 mL/min改變血液流量之四種溶質廓清率實驗值與理論曲線 37
圖- 12 透析器180在QF=0 mL/min及QD=500 mL/min改變血液流量之四種溶質廓清率實驗值與理論曲線 37
圖- 13 透析器160在QF=0 mL/min及QB=200 mL/min改變透析液流量之四種溶質廓清率實驗值與理論曲線 39
圖- 14 透析器180在QF=0 mL/min及QB=200 mL/min改變透析液流量之四種溶質廓清率實驗值與理論曲線 40
圖- 15 體外模擬透析控制組、鐵質透析液及鐵質與EGCG透析液，血液中FRAP與時間之關係 42
圖- 16 體外模擬透析控制組、鐵質透析液及鐵質與EGCG透析液，血液中TBARS與時間之關係 43

附圖- 1 FRAP標準曲線 58
附圖- 2 TBARS標準曲線 61

表索引
表- 1 依化學成份之薄膜材質分類 8
表- 2 實驗設備/耗材 20
表- 3 實驗試劑/標準品 21
表- 4 檢驗試劑 21
表- 5 實驗藥品 22
表- 6 國內研發兩型中空纖維透析器規格 22
表- 7 測試溶液之溶質濃度 24
表- 8 透析器160在QF=0 mL/min及QD=500 mL/min改變血液流量之廓清率及平均K0A值 34
表- 9 透析器180在QF=0 mL/min及QD=500 mL/min改變血液流量之廓清率及平均K0A值 34
表- 10 透析器160在QF=16.7 mL/min及QD=500 mL/min改變血液流量之廓清率 35
表- 11 透析器180在QF=16.7 mL/min及QD=500 mL/min改變血液流量之廓清率 36
表- 12 透析器160在QF=0 mL/min及QB=200 mL/min改變透析液流量之廓清率 38
表- 13 透析器180在QF=0 mL/min及QB=200 mL/min改變透析液流量之廓清率 39

附表- 1 FRAP標準曲線數值 58
附表- 2 模擬透析控制組血液進口端FRAP檢測數值 59
附表- 3 模擬透析鐵質透析液血液進口端FRAP檢測數值 59
附表- 4 模擬透析鐵質與EGCG透析液血液進口端FRAP檢測數值 60
附表- 5 TBARS標準曲線數值 61
附表- 6 模擬透析控制組血液進口端TBARS檢測數值 62
附表- 7 模擬透析鐵質透析液血液進口端TBARS檢測數值 62
附表- 8 模擬透析鐵質與EGCG透析液血液進口端TBARS檢測數值 63

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