The Culprit of Gout: Triggering Factors and Formation of Monosodium Urate Monohydrate

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题名:	The Culprit of Gout: Triggering Factors and Formation of Monosodium Urate Monohydrate
作者:	池孟修;Chih,Meng-Hsiu
贡献者:	化學工程與材料工程學系
关键词:	痛風;尿酸單鈉鹽;玻尿酸;尿酸;gout;monosodium urate monohydrate;hyaluronate;uric acid dihydrate
日期:	2015-07-29
上传时间:	2015-09-23 10:50:09 (UTC+8)
出版者:	國立中央大學
摘要:	痛風是一種常見尿酸鈉鹽結晶引發的關節炎。據估計全世界至少有2.5%的人深受痛風所苦。高尿酸血症為現今醫學公認引發痛風的主因，但是只有少部分高尿酸血症患者會出現痛風的症狀。而且，目前對於尿酸鈉鹽於人體的形成機制尚未明朗。因此，本篇論文將有四大研究目標，以試圖解開痛風形成之謎。第一，觀察尿酸鈉鹽結晶於不同鈉離子溶液中的形成與成長。第二，研究尿酸晶體在仿生溶液中轉化成尿酸鈉鹽之過程，並且找出pH值與痛風形成之關聯性。第三，瞭解玻尿酸與體內常見陽離子之反應，以及其對於尿酸鈉鹽結晶之影響。第四，檢測20種人體常見胺基酸對尿酸鈉鹽結晶的影響。依據實驗結果與相關文獻參照，本論文提出八項重要發現：(1) 在人體條件下，只需要調整溶液的鈉離子濃度即可製備出不同形貌的尿酸鈉鹽結晶分別為球晶、海膽狀結晶與蝴蝶結狀團聚；(2)尿酸鈉鹽結晶之成長演進，依序從球晶、海膽狀結晶到最後形成蝴蝶結狀團聚；(3)球晶為所有尿酸鹽晶型的前驅型態；(4)藉由玻尿酸、鈉離子與鈣離子溶液，我們觀察到全新形貌的尿酸鈉鹽；(5)我們藉由降低溶液的pH值促使尿酸結晶沉澱，並且觀察尿酸結晶於仿生液中轉化為尿酸鈉鹽之過程；(6)尿酸的轉化可以解釋醫學上對於痛風相關發現，我們進而提出痛風於人體真正的發病機制；(7)我們提出玻尿酸鏈、鈣離子與尿酸離子會形成複合物藉此抑制尿酸鈉鹽之形成。而且可以說明為何只有少數的高尿酸血症患者會罹患痛風；和(8)某些特定的氨基酸能夠抑制尿酸鈉鹽的形成。 ;Gout is the most widespread crystal-induced inflammatory arthritis by monosodium urate monohydrate (MSUM). It was estimated at least 2.5% people suffering from it all over the world. Hyperuricemia is essential for the MSUM formation, but only some of patients are able to develop gout. Therefore, there are 4 aims in the research to reveal the mystery of MSUM formation in vivo: First, to produce beachballs and other MSUM morphologies with various Na+ ions level which will unravel the pathogenesis of gout. Second, to observe the conversion from uric acid to MSUM in the simulated body fluid system. Third, to explore the synergistic effect of hyaluronate, Na+ ion and Ca2+ ion in MSUM crystallization. Forth, to find the influence of the common 20 kinds of amino acid in human body on MSUM crystallization. According to the experimental results and reference, we proposed 8 significant findings in this study: various morphologies of MSUM: (1) beachball, spherulite and bow-like aggregate could be prepared at different Na+ ion levels at 37C, (2) morphological transformation from beachball to spherulite to bow-like aggregate can be achieved, (3) beachball is a disordered, first-formed precursor for all MSUM morphologies, (4) a new type of MSUM fishtail morphology was observed in the hyaluronate, Na+ and Ca2+ ion containing solutions, (5) the dilemma of MSUM deposition at thermodynamically unfavorable low pH condition was solved by the newly discovered kinetic pathway for the phase conversion of uric acid dihydrate (UAD) to MSUM, (6) the UAD-to-MSUM pathway can also be used to explain the effects brought about by the inflammatory response and acidosis, and why MSUM deposition in cartilage and connective tissue, (7) the question of why only a fraction of hyperuricemic patients has gout was answered by the solubilization of urate through the complex formation with hyaluronate chains and Ca2+ ions, and (8) some amino acids can influence the size of MSUM crystal.
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