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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 林思洸 | |
dc.contributor.author | Ting-Yi Wu | en |
dc.contributor.author | 吳庭宜 | zh_TW |
dc.date.accessioned | 2021-06-08T03:01:27Z | - |
dc.date.copyright | 2017-09-08 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-07-24 | |
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Thompson, Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science, 2009. 324(5930): p. 1029-33. 51. Aktan, F., iNOS-mediated nitric oxide production and its regulation. Life Sci, 2004. 75(6): p. 639-53. 52. Surh, Y.J., et al., Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res, 2001. 480-481: p. 243-68. 53. Bosco, M.C., et al., Hypoxia modifies the transcriptome of primary human monocytes: modulation of novel immune-related genes and identification of CC-chemokine ligand 20 as a new hypoxia-inducible gene. J Immunol, 2006. 177(3): p. 1941-55. 54. Levitan, I., S. Volkov, and P.V. Subbaiah, Oxidized LDL: diversity, patterns of recognition, and pathophysiology. Antioxid Redox Signal, 2010. 13(1): p. 39-75. 55. 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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/20745 | - |
dc.description.abstract | 類風溼性關節炎是一種由多種細胞(包含巨噬細胞, 關節滑膜細胞,內皮細胞, 其他免疫細胞)共同調控的系統性疾病。發炎的缺氧環境會活化類風溼性關節炎滑液細胞(RASF),分泌出多種cytokine和 matrix metalloproteinase,造成更嚴重的發炎和周邊組織的破壞分解。類風溼性關節炎也是心血管疾病的危險因子。在病患的關節滑液中發現與atheroma有類似的細胞組成。OxLDL和27-hydroxycholesterol會加劇粥狀動脈硬化。本實驗希望探討巨噬細胞在模擬關節炎缺氧環境下對 sterol 27-hydroxylase (CYP27A1)的調控,SIRT5在巨噬細胞的變化,RASF是否會受到27-hydroxycholesterol的影響。實驗結果發現,在MonoMac 6細胞在受到缺氧刺激下,iNOS和COX-2的蛋白表現上升,CYP27A1的蛋白表現量下降。在SIRT5 overexpressed MonoMac 6細胞CYP27A1會上升。受缺氧刺激時發現,iNOS和COX-2沒有明顯變化,CYP27A1的蛋白表現量下降。27HC會促進RASF細胞的增生;但會造成U2OS細胞存活率下降。在合併缺氧與27HC刺激下,RASF分泌CCL20的量會上升。U2OS細胞分泌CCL20的量沒有明顯差異。總結上述的發現,缺氧刺激會使巨噬細胞產生與發炎相關的酵素,CYP27A1下降,可能影響正常膽固醇排出的機制。低劑量的27HC會促使RASF增生但不利骨細胞的生長。27HC也會使RASF分泌更多CCL20,造成chemotaxis。 | zh_TW |
dc.description.abstract | Rheumatoid arthritis is a systemic disease regulated by different cells including macrophage, synovial fibroblast, endothelial cell and other immune cells. Inflammation related hypoxia activates rheumatoid arthritis fibroblast (RASF), resulting in cytokines and matrix metalloproteinase secretion that cause persistent chronic inflammation and destruction of surrounding tissues. Rheumatoid arthritis is one of the risk factor of cardiovascular disease. Cells extracted from synovial fluid of RA patient revealed similar composition with atherosclerosis. OxLDL and 27-hydroxycholesterol deteriorate atherosclerosis. The purpose of this study is to investigate how sterol 27-hydroxylase(CYP27A1) and sirtuin5(SIRT5) regulate macrophage metabolism under hypoxia. And the relationship of 27HC and RASF. In this study, expression of iNOS and COX-2 increased while CYP27A1 and SIRT5 decreased in MonoMac 6 cell under hypoxia Expression of CYP27A1 increased in SIRT5 overexpressed MonoMac 6 cell. No significant differences of iNOS and COX-2 expression in SIRT5 overexpressed MonoMac 6 copared under hypoxia compared to normxia whereas CYP27A1 decreased and SIRT5 expression increased.27HC promoted RASF proliferation but promoted U2OS cell death. Expression of CCL20 increased in RASF under 27HC and hypoxia while there was no significant differences in U2OS cell. In summary, macrophage secreted proinflammatory related enzyme and decreased CYP27Al level under hypoxia that might related to impared cholesterol efflux mechanism.Low-dosed 27HC might promote RASF proliferation and CCL20 expression. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T03:01:27Z (GMT). No. of bitstreams: 1 ntu-106-R03422006-1.pdf: 1979200 bytes, checksum: 4f5c61a66dfefd0e164f2c0d22f896ac (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 口試委員審定書 i
謝誌 ii 中文摘要 iii 英文摘要 iv 第一章導論 4 1.1 類風溼性關節炎 4 1.2類風溼性關節炎的細胞變化 4 1.2.1 RASF的活化 4 1.2.2 發炎細胞的活化 5 1.2.3 先天性免疫的影響 5 1.3類風溼性關節炎與肥胖的關係 6 1.3.1肥胖與關節炎的關係 6 1.3.2 肥胖與關節炎的致病機制 6 1.4膽固醇在人體內的恆定 7 1.4.1膽固醇 7 1.4.2 LXRs 7 1.4.3 SRPBPs 7 1.4.4 LXRs與SRPBPs的調節 7 1.5OxLDL 8 1.5.1 OxLDL的組成 8 1.5.2 invivo產生的Oxidized LDL 8 1.5.3 invivo產生的氧化劑 9 1.6Oxysterol 扮演的腳色 10 1.6.1 oxysterol 10 1.6.2 Sterol 27-hdroxylase 10 1.7 OxLDL與類風濕性關節炎的關係 11 1.7.1類風溼性關節炎的相關疾病機轉 11 1.7.2 OxLDL 在類風溼性關節炎的表現 12 1.7.3 LOX-1與關節炎的關係 12 1.8SIRT5 扮演的腳色 12 1.8.1 Sirtuins簡介 12 1.8.2 Sirtuins 在細胞內的位置與酵素 13 1.8.3 Sirtuins 在粒線體的表現 13 1.8.4 SIRT5 在粒線體的功能 14 1.8.5 SIRT5, CYP27A1和關節炎的關係 14 第二章 實驗目的 15 第三章材料與方法 16 3.1 實驗細胞株 16 3.2 細胞存活率分析 (MTT assay) 16 3.2.1 RASF細胞對27HC之增生率分析 16 3.2.2 U2OS細胞對27HC之存活率分析 16 3.3蛋白質的萃取 17 3.4西方點墨法(Western blot) 18 3.5 缺氧環境對MonoMac 6細胞在發炎反應和Cyp27A1的影響 19 3.5.1 CoCl2模擬缺氧環境對MonoMac 6細胞的影響 19 3.5.2不同時間點 CoCl2模擬缺氧環境對MonoMac 6細胞的影響 19 3.5.3 CoCl2缺氧環境對SIRT-5 overexpressed MonoMac 6細胞的影響 20 3.6 27HC以及缺氧環境對RASF和U2OS對CCL20的影響 20 3.7 OxLDL對RASF細胞的CYP27A1的影響 21 3.7.1 OxLDL的製備 21 3.7.2OxLDL 對Cyp27A1在RASF細胞, RASF-Flag, SIRT5 overexpressed RASF的變化 21 第四章實驗結果 22 4.1缺氧刺激對MonoMac 6 細胞的影響 22 4.1.1缺氧濃度影響iNOS, COX-2, CYP27A1, SIRT5在MonoMac 6的蛋白表現 22 4.1.2缺氧時間影響iNOS, COX-2, CYP27A1, SIRT5在MonoMac 6的蛋白表現 22 4.1.3缺氧影響iNOS, COX-2, CYP27A1在SIRT5 overexpressed MonoMac 6的蛋白表現 22 4.2缺氧和27-hydroxycholesterol對RASF 細胞的影響 23 4.2.1 27-hydroxycholesterol對RASF細胞增生率的影響 23 4.2.2缺氧合併27-Oxycholesterol對CCL20在 RASF細胞的影響 23 4.2.3 OxLDL增加 RASF細胞CYP27A1的表現 24 4.3缺氧和27-hydroxycholesterol對U2OS 細胞的影響 24 4.3.1 27-hydroxycholesterol對U2OS細胞存活率的影響 24 4.3.2缺氧合併27-hydroxycholesterol對CCL20在 U2OS細胞的影響 24 第五章討論 25 5.1 缺氧對macrophage細胞的影響 25 5.2 27-hydroxycholesterol對RASF細胞的影響 27 5.3 27-hydroxycholesterol對U2OS細胞的影響 28 參考文獻 29 附錄 35 | |
dc.language.iso | zh-TW | |
dc.title | 肥胖加劇關節炎病情:作用機轉探討及未來發展臨床醫療方針的可能性 | zh_TW |
dc.title | Obesity Exacerbates Arthritis Progression: Mechanisms and Therapeutic Potential | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 郭生興,洪志遠 | |
dc.subject.keyword | 類風溼性關節炎,OxLDL,27-hydroxycholesterol, | zh_TW |
dc.subject.keyword | rheumatoid arthritis,OxLDL,27-hydroxycholester, | en |
dc.relation.page | 46 | |
dc.identifier.doi | 10.6342/NTU201701632 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2017-07-24 | |
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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