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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林思洸(Sze-Kwan Lin) | |
| dc.contributor.author | Chi-Hung Chen | en |
| dc.contributor.author | 陳奇宏 | zh_TW |
| dc.date.accessioned | 2021-06-17T08:16:24Z | - |
| dc.date.available | 2024-08-26 | |
| dc.date.copyright | 2019-08-26 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-08-14 | |
| dc.identifier.citation | 1. Sivakumar B, Akhavani MA, Winlove CP, Taylor PC, Paleolog EM, Kang N. Synovial hypoxia as a cause of tendon rupture in rheumatoid arthritis. J Hand Surg Am 2008;33(1):49-58.
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Neumann, E., S. Gay, and U. Muller-Ladner, The RANK/RANKL/osteoprotegerin system in rheumatoid arthritis: new insights from animal models. Arthritis Rheum, 2005. 52(10): p. 2960-7. 15. Symmons, D.P. and S.E. Gabriel, Epidemiology of CVD in rheumatic disease,with a focus on RA and SLE. Nat Rev Rheumatol, 2011. 7(7): p. 399-408. 16. Crowson, C.S., et al., Contribution of obesity to the rise in incidence of rheumatoid arthritis. Arthritis Care Res (Hoboken), 2013. 65(1): p. 71-7. 17. Neumann, E., et al., Adipocytokines as driving forces in rheumatoid arthritis and related inflammatory diseases? Arthritis Rheum, 2011. 63(5): p. 1159-69. 18. Stryer, Lubert. Biosynthesis of membrane lipids and steroids. In: Biochemistry, Fourth ed. 1995. New York: W.H. Freeman and Company. pp. 697–700. 19. Schroepfer, G.J., Jr., Oxysterols: modulators of cholesterol metabolism and other processes. Physiol Rev, 2000. 80(1): p. 361-554. 20. Lin, Y.Y. and L.L. Smith, Sterol metabolism. 28. 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Holmberg, Oxidation of 5 beta-cholestane-3 alpha,7 alpha, 12 alpha-triol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid by cytochrome P-450(26) from rabbit liver mitochondria. Biochem Biophys Res Commun, 1990. 167(2): p. 391-5. 26. Cali, J.J., et al., Mutations in the bile acid biosynthetic enzyme sterol 27- hydroxylase underlie cerebrotendinous xanthomatosis. J Biol Chem, 1991. 266(12): p. 7779-83. 27. Babiker, A., et al., Elimination of cholesterol as cholestenoic acid in human lung by sterol 27-hydroxylase: evidence that most of this steroid in the circulation is of pulmonary origin. J Lipid Res, 1999. 40(8): p. 1417-25. 28. Nelson ER, Wardell SE, et al. 27-hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science. 342(6162):1094-8. 29. Anastrozole. The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016. 30. Simpson ER. Sources of estrogen and their importance. J. Steroid Biochem. Mol. Biol. 2003;86(3–5):225–30. 31. Wang T, Arifoglu P, Ronai Z, Tew KD. Glutathione S-transferase singaling through interaction with the C terminus. J Biol Chem. 2001;276(24):20999-21003. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74002 | - |
| dc.description.abstract | 類風濕性關節炎是一種與多種細胞相關的全身性疾病，包括單核細胞，滑
膜細胞，內皮細胞和其他免疫細胞。類風濕性關節炎可能是心血管疾病的因子之一，因為在患者的關節滑液中發現與動脈粥樣化有相似的細胞組成，而27-羥基膽固醇(27-hydroxycholestrol, 27-HC)加劇動脈粥樣硬化。在關節炎的進程中，類風濕性關節炎滑膜纖維母細胞(rheumatoid arthritis synovial fibroblast, RASF)扮演重要的角色。本實驗希望藉由研究RASF 細胞是否會受到27-HC 的影響，以延伸探討肥胖和膽固醇代謝對類風濕性關節炎的影響。結果發現，27-HC 促進RASF 細胞的增殖，以及它會造成發炎介質(chemokine (C-C motif) ligand 2, CCL2)濃度的增加。在動物實驗中，我們發現高脂高膽固醇飲食及卵巢切除確實可以增加27-HC 在血漿中的濃度，進而加劇關節炎的進展，例如：發炎細胞的浸潤和滑膜細胞的增殖；而使用CYP27A1 抑制劑—阿那曲唑(anastrozole)的大鼠會減少關節炎的症狀。因此我們可以推測27-HC 會加劇類風濕性關節炎的進程。 | zh_TW |
| dc.description.abstract | Rheumatoid arthritis (RA) is a systemic disease that is regulated by multiple varieties of cells, including monocytes, synovial cells, endothelial cells and other immune cells. RA is also a risk factor for cardiovascular disease. A similar cellular composition to atheroma was found in the synovial fluid of the patient. 27-hydroxycholesterol (27-HC) exacerbates atherosclerosis. In arthritis, rheumatoid arthritis synovial cells (RASF) plays an important role in the process of RA. This experiment hopes to investigate whether RASF will be affected by 27-HC to explore obesity and cholesterol metabolism for rheumatoid arthritis impact. The result shows that 27-HC promoted the proliferation of RASF cells; caused an increase in the concentration of various inflammatory mediators. In animal experiments, it is found that the high fat diet can indeed aggravate the development of arthritis, the infiltration of inflammatory cells and the proliferation of synovial cells, while the rats used the anastrozole which is an inhibitor of CYP27A1 reduce symptoms of fatty liver and arthritis. As a result, we may conclude that 27-HC could exacerbate the progression of rheumatoid arthritis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T08:16:24Z (GMT). No. of bitstreams: 1 ntu-108-R05422005-1.pdf: 1613516 bytes, checksum: 06da0ad03a7943c8813dbb9c630f5c11 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 中文摘要 i
Abstract ii 目錄 iii 圖目錄 vii 表目錄 viii 第一章 導論 1 1.1 類風溼性關節炎簡介 1 1.2 類風溼性關節炎的細胞變化 2 1.2.1 發炎細胞的活化 2 1.2.2 類風濕性關節炎滑膜纖維母細胞的活化 2 1.3 類風溼性關節炎與肥胖的關係 3 1.4 膽固醇在人體中的代謝與恆定 5 1.5 氧固醇的生成及扮演的角色 5 1.5.1 氧固醇(oxysterol) 5 1.5.2 固醇27-羥化酶(sterol 27-hydroxylase) 6 1.5.3 27-羥基膽固醇的組成 7 1.6 阿那曲唑與膽固醇的關係 8 第二章 實驗目的 9 第三章 材料與方法 10 3.1 實驗細胞株 10 3.2 細胞繁殖速率分析 11 3.2.1 細胞計數 11 3.3 酵素免疫分析法(Enzyme-linked immunosorbent assay, ELISA) 11 3.3.1 Chemokine (C-C motif) ligand 2 (CCL2) 11 3.3.2 27-羥基膽固醇(27-hydroxycholesterol, 27-HC) 13 3.4 西方點墨法(Western blot) 15 3.4.1 蛋白質萃取 16 3.4.2 蛋白質定量 16 3.4.3 十二烷基硫酸鈉聚丙烯酰胺凝膠電泳(sodium dodecyl sulfate polyacrylamide gel electrophoresis, SDS-PAGE) 17 3.4.4 轉漬(transfer)及封閉(blocking) 17 3.4.5 一級抗體與二級抗體的檢測 17 3.5 關節炎動物模式 18 3.6 免疫組織化學染色法 19 3.7 組織學分析 20 第四章 實驗結果 21 4.1 27-羥基膽固醇對RASF細胞增生率的影響 21 4.2 27-羥基膽固醇對RASF細胞釋出發炎介質的影響 21 4.3 27-羥基膽固醇對J774細胞的影響 21 4.3.1 27-羥基膽固醇影響iNOS在J774細胞的蛋白表現 21 4.3.2 27-羥基膽固醇影響COX-2在J774細胞的蛋白表現 22 4.3.3 27-羥基膽固醇影響Arg-1在J774細胞的蛋白表現 22 4.4 棕櫚酸與膽固醇對J774、HepG2、HCT116細胞的影響 22 4.4.1 棕櫚酸與膽固醇刺激對於J774細胞lysate中27-羥基膽固醇含量的影響 22 4.4.2 棕櫚酸與膽固醇刺激對於HepG2細胞lysate中27-羥基膽固醇含量的影響 22 4.4.3 棕櫚酸與膽固醇刺激對於HCT116細胞lysate中27-羥基膽固醇含量的影響 23 4.5 動物實驗 23 4.5.1 不同條件下，大鼠血漿中27-羥基膽固醇的濃度 23 4.5.2 不同條件下，大鼠腳掌的厚度 24 4.5.3 不同條件下，組織切片中類風濕性關節炎組織病理嚴重程度 24 4.5.4 不同條件下，組織切片中蘇木精-伊紅染色的比較 24 4.5.5 不同條件下，組織切片中免疫組織化學染色的比較 24 第五章 討論 26 5.1 27-羥基膽固醇對RASF細胞的影響 26 5.2 27-羥基膽固醇對J774細胞的影響 26 5.3 推測27-羥基膽固醇的來源 27 5.4 阿那曲唑與27-羥基膽固醇的關係 27 第六章 結論 28 參考資料 29 圖片 34 表格 49 圖目錄 圖1、27-羥基膽固醇促進RASF細胞增生率 34 圖2、RASF細胞釋出發炎介質(CCL2)隨著27-羥基膽固醇的濃度增加而增加 35 圖3、RASF細胞釋出發炎介質隨著27-羥基膽固醇作用的時間增加而增加 36 圖4、27-羥基膽固醇增加iNOS在J774細胞的蛋白表現 37 圖5、27-羥基膽固醇增加COX-2在J774細胞的蛋白表現 38 圖6、27-羥基膽固醇降低Arg-1在J774細胞的蛋白表現 39 圖7、棕櫚酸與膽固醇刺激對於J774、HepG2、HCT116細胞lysate中27-羥基膽固醇含量的影響 40 圖8、阿那曲唑可以降低大鼠血漿中27-HC的濃度 42 圖9、阿那曲唑對於大鼠腳掌的厚度的影響不明顯 43 圖10、阿那曲唑可以降低組織切片中類風濕性關節炎組織病理嚴重程度 44 圖11、組織切片中蘇木精-伊紅染色的比較 45 圖12、組織切片中免疫組織化學染色(CD68)的比較 46 圖13、組織切片中免疫組織化學染色(iNOS)的比較 47 圖14、組織切片中免疫組織化學染色(Arg-1)的比較。 48 表目錄 表1、蛋白質萃取液 49 表2、10 %的分離膠體 49 表3、集膠膠體 49 表4、4X Sample loading dye 50 表5、一級抗體比例 50 表6、二級抗體比例 51 | |
| dc.language.iso | zh-TW | |
| dc.title | 27-羥基膽固醇加劇類風溼性關節炎的進程 | zh_TW |
| dc.title | 27-hydroxycholesterol Exacerbates the Progression of
Rheumatoid Arthritis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 洪志遠,郭生興 | |
| dc.subject.keyword | 類風溼性關節炎,27-羥基膽固醇,阿那曲唑, | zh_TW |
| dc.subject.keyword | rheumatoid arthritis,27-hydroxycholesterol,anastrozole, | en |
| dc.relation.page | 51 | |
| dc.identifier.doi | 10.6342/NTU201903406 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2019-08-15 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 臨床牙醫學研究所 | zh_TW |
| 顯示於系所單位： | 臨床牙醫學研究所 | |
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