臺灣博碩士論文加值系統

國內罹患高尿酸血症的人口近年來逐漸增加，其中又以青壯年的罹患者最多，而且有越來越年輕化的趨勢。研究報告指出，高尿酸血症除會導致大家耳熟能詳的痛風外，也與肥胖、高血脂、高血壓、糖尿病、心臟病及腦血管病變等慢性疾病息息相關。因此，是個非常值得國人注意的健康問題。高尿酸血症的患者中只有10％ 表現出痛風關節炎的症狀；反之，高尿酸血症在大部份患者身上是造成心臟及腎臟的損傷。山藥因為具有清虛熱于肺脾，補脾固「腎」的性質而被中醫認為對痛風或高尿酸的改善可能有幫助。本實驗室曾以山藥餵食正常老鼠，結果發現山藥的攝取會降低老鼠血液中的尿酸值並改善氧化壓力，因而同意山藥對高尿酸血症的控制應該有幫助。但是，該研究是使用正常老鼠而非高尿酸的動物模式，而且只用了一個品種的山藥，也未探討山藥對腎功能的影響。所以將以高尿酸的動物模式檢測山藥保護腎臟及降尿酸的效果，採用三個山藥品種以比較其差異，並分析黃嘌呤氧化酶及黃嘌呤去氫酶的活性以探討其生化證據。
在本次的研究中，將對關於山藥的應用提供新的發現，其中包含哪一種山藥具有降低尿酸及維持腎臟的功能，以用於促進山藥的培育及商業功用。

Hyperuricemia is a getting severe healthy problem in Taiwan because it is strongly associated with diabetes, obesity, hypertension. In most patients, hyperuricemia leads to enhanced oxidation and inflammation, and finally causes cardiac and kidney damage. Ancient Chinese medicine indicated that Dioscorea spp. with special benefit to kidney may provide protective and therapeutic effect to improve hyperuricemia.
Our past study has found that the intake of Dioscorea spp. could effectively reduce plasma uric acid level in normal mice, thus we think this food is helpful for patient with hyperuricemia. However, we used only one kind of Dioscorea spp.. We wish to study the protective and therapeutic effect of Dioscorea spp. in hyperuricemia by using three species of Dioscorea spp.. In this study, the influence of Dioscorea spp. intake upon the activity of xanthine oxidase, oxidative and inflammatory stress, as well as the kidney function will be examined.
The results of this study will provide new findings regarding the application of Dioscorea spp., including the information of specie for reducing uric acid level and maintaining kidney function. These data can be used for promoting cultivation, and business of Dioscorea spp..

目次……………………………………………………………………………I
中文摘要………………………………………………………………………VI
英文摘要………………………………………………………………………VII
第一章 前言……………………………………………………………………1
第二章 文獻探討………………………………………………………………2
一、山藥………………………………………………………………………2
（一）概論…………………………………………………………………2
（二）種類…………………………………………………………………2
（三）成分特性……………………………………………………………3
（四）保健功能及藥理作用………………………………………………4
二、痛風與高尿酸血症………………………………………………………5
（一）尿酸代謝……………………………………………………………5
（二）高尿酸血症的成因…………………………………………………9
（三）高尿酸血症臨床症狀………………………………………………9
（四）高尿酸血症之治療…………………………………………………10
三、丙二醛……………………………………………………………………11
四、麩胱苷肽過氧化酶………………………………………………………12
五、麩胱苷肽…………………………………………………………………12
第三章 研究目的………………………………………………………………14
第四章 實驗材料與方法………………………………………………………15
一、實驗材料…………………………………………………………………15
（一）實驗動物……………………………………………………………15
（二）化學試藥……………………………………………………………15
（三）設備儀器……………………………………………………………17
二、實驗方法…………………………………………………………………18
（一）實驗設計……………………………………………………………18
（二）實驗原料及飼料配置………………………………………………19
（三）Oxonic Acid potassium salt…………………………………………20
（四）動物血液及臟器收集………………………………………………20
三、實驗分析…………………………………………………………………21
（一）尿酸（Uric Acid）測定………………………………………… 21
（二）黃嘌呤氧化酶（Xanthine Oxidase）測定…………………………21
（三）黃嘌呤去氫酶（Xanthine Dehydrogenase）測定…………………22
（四）總蛋白質（Total Protein）濃度測定………………………………23
（五）脂質過氧化（Thiobarbituric acid reactive substances；TBARs）測定
………………………………………………………………………23
（六）麩胱苷肽過氧化酶（Glutathione peroxidase；GPx）活性測定…24
（七）麩胱苷肽（Glutathione；GSH）濃度測定……………………… 25
（八）肌酸酐（Creatinine；Cr）濃度測定…………………………… 25
（九）Renal organic ion transporter mRNA測量…………………………26
四、統計分析…………………………………………………………………27
第五章 實驗結果………………………………………………………………28
第六章 討論……………………………………………………………………32
第七章 結論……………………………………………………………………35
第八章 參考文獻………………………………………………………………67




圖 表 目 次
表1.離子通道系統分類介紹……………………………………………………7
表2.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其體
重變化………………………………………………………………………37
表3.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之飼
料後小鼠其體重變化………………………………………………………38
圖1.尿酸塩代謝恆定路徑………………………………………………………6
圖2.尿酸塩在腎臟近曲小管細胞離子通道交換情形…………………………9
圖3. Allopurinol藥物代謝路徑…………………………………………………11
圖4.麩胱苷肽氧化還原反應途徑………………………………………………13
圖5.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其血
清尿酸值之影響……………………………………………………………39
圖6.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其肝
臟尿酸值之影響……………………………………………………………40
圖7.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其肝
臟黃嘌呤氧化酶之影響……………………………………………………41
圖8.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其肝
臟黃嘌呤去氫酶之影響……………………………………………………42
圖9.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其血
清脂質過氧化之影響………………………………………………………43
圖10.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其肝
臟脂質過氧化之影響………………………………………………………44
圖11.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其腎
臟脂質過氧化之影響……………………………………………………45
圖12.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其血
清麩胱苷肽過氧化酶活性之影響………………………………………46
圖13.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其肝
臟麩胱苷肽過氧化酶活性之影響………………………………………47
圖14.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其血
清麩胱苷肽濃度之影響…………………………………………………48
圖15.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其血
清肌酸酐濃度之影響……………………………………………………49
圖16.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其腎
臟Organic anion tranporter 1 mRNA之表現情形………………………50
圖17.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其腎
臟Organic anion tranporter 3 mRNA之表現情形………………………51
圖18.餵食一週含有不同濃度及品系山藥的飼料後以Oxonic acid誘發之小鼠其腎
臟Organic cation tranporter 2 mRNA之表現情形………………………52
圖19.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之
飼料後小鼠其血清尿酸值之影響…………………………………………53
圖20.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之
飼料後小鼠其肝臟尿酸值之影響…………………………………………54
圖21.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之
飼料後小鼠其肝臟黃嘌呤氧化酶之響……………………………………55
圖22.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之
飼料後小鼠其肝臟黃嘌呤去氫酶之響……………………………………56
圖23.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之
飼料後小鼠其血清脂質過氧化之影響……………………………………57
圖24.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之
飼料後小鼠其肝臟脂質過氧化之影響……………………………………58
圖25.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之
飼料後小鼠其腎臟脂質過氧化之影響……………………………………59
圖26.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之
飼料後小鼠其血清麩胱苷肽過氧化酶活性之影響………………………60
圖27.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之
飼料後小鼠其肝臟麩胱苷肽過氧化酶活性之影響………………………61
圖28.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之
飼料後小鼠其血清麩胱苷肽濃度之影響…………………………………62
圖29.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之
飼料後小鼠其血清肌酸酐濃度之影響……………………………………63
圖30.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之
飼料後小鼠其腎臟Organic anion tranporter 1 mRNA之表現情形………64
圖31.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之
飼料後小鼠其腎臟Organic anion tranporter 3 mRNA之表現情形………65
圖32.餵食一週、三週、七週含有不同濃度及品系山藥與2% Oxonic acid製成之
飼料後小鼠其腎臟Organic cation tranporter 2 mRNA之表現情形………66

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