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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 姚宗珍 | zh_TW |
| dc.contributor.advisor | Chung-Chen Yao | en |
| dc.contributor.author | 林奕安 | zh_TW |
| dc.contributor.author | Yi-An Lin | en |
| dc.date.accessioned | 2023-05-19T08:56:11Z | - |
| dc.date.available | 2023-11-10 | - |
| dc.date.copyright | 2023-10-03 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-05-08 | - |
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Lab Invest. 2003;83(4):579-588. 52. Szekanecz Z, Strieter RM, Kunkel SL, Koch AE. Chemokines in rheumatoid arthritis. Springer Semin Immunopathol. 1998;20(1-2):115-132. 53. Matcham F, Rayner L, Steer S, Hotopf M. The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology (Oxford). 2013;52(12):2136-2148. 54. Waraich P, Goldner EM, Somers JM, Hsu L. Prevalence and incidence studies of mood disorders: a systematic review of the literature. Can J Psychiatry. 2004;49(2):124-138. 55. VanDyke MM, Parker JC, Smarr KL, et al. Anxiety in rheumatoid arthritis. Arthritis Rheum. 2004;51(3):408-412. 56. Shin SY, Katz P, Wallhagen M, Julian L. Cognitive impairment in persons with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64(8):1144-1150. 57. Vergne-Salle P, Pouplin S, Trouvin AP, et al. The burden of pain in rheumatoid arthritis: Impact of disease activity and psychological factors. Eur J Pain. 2020;24(10):1979-1989. 58. Wallin K, Solomon A, Kåreholt I, Tuomilehto J, Soininen H, Kivipelto M. Midlife rheumatoid arthritis increases the risk of cognitive impairment two decades later: a population-based study. J Alzheimers Dis. 2012;31(3):669-676. 59. Nishioku T, Yamauchi A, Takata F, et al. Disruption of the blood-brain barrier in collagen-induced arthritic mice. Neurosci Lett. 2010;482(3):208-211. 60. Lang SC, Harre U, Purohit P, et al. Neurodegeneration Enhances the Development of Arthritis. J Immunol. 2017;198(6):2394-2402. 61. Andersson KME, Wasén C, Juzokaite L, et al. Inflammation in the hippocampus affects IGF1 receptor signaling and contributes to neurological sequelae in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2018;115(51):E12063-E12072. 62. Park SM, Shin JH, Moon GJ, Cho SI, Lee YB, Gwag BJ. Effects of collagen-induced rheumatoid arthritis on amyloidosis and microvascular pathology in APP/PS1 mice. BMC Neurosci. 2011;12:106. 63. Lopes F, Vicentini FA, Cluny NL, et al. Brain TNF drives post-inflammation depression-like behavior and persistent pain in experimental arthritis. Brain Behav Immun. 2020;89:224-232. 64. Sood M, Lee JC, Avivi-Arber L, Bhatt P, Sessle BJ. Neuroplastic changes in the sensorimotor cortex associated with orthodontic tooth movement in rats. J Comp Neurol. 2015;523(10):1548-1568. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/87411 | - |
| dc.description.abstract | 免疫細胞及各種Cytokines、Chemokines和MMPs皆參與調控系統性發炎疾病 (如類風濕性關節炎) 與區域性發炎反應 (如牙齒矯正移動)，因此本研究試圖探討「系統性的發炎疾病」與「局部刺激的發炎反應」兩者之間的交互作用及關係。
本實驗使用Mmp-3 promoter-Luciferase-emGfp之基因轉殖大鼠模型，分別單獨以膠原蛋白誘導關節炎21天、牙齒矯正14天、或二者合併的刺激21天，定時在麻醉下使用非侵入式活體光學影像系統 (In vivo imaging system) 觀察各部位MMP-3的冷光訊號變化、抽血檢測血清內各項Cytokines和Chemokines濃度變化、犧牲時以微電腦斷層掃描儀 (Micro CT image) 測量牙齒移動之距離差異後，製作標本切片及免疫螢光染色觀察MMP-3、Iba-1、GFAP等神經發炎指標在大腦皮質和海馬迴的表現。 實驗結果顯示各組在裝設矯正器後第1天的口內冷光訊號皆顯著提升，但關節炎合併矯正組別的口內冷光訊號與單純矯正組別無顯著差異。而單純關節炎組別以及關節炎合併矯正組別的血清內發炎因子濃度皆呈雙波峰型態，但合併組在第二次波峰的上升量與單純關節炎組無顯著差異。在大腦皮質和海馬迴的MMP-3、Iba-1、GFAP免疫螢光染色訊號，單純關節炎組與合併組皆大於生理食鹽水控制組，但單純關節炎組與合併組無統計顯著差異。 本研究結果推判系統性發炎不會影響局部牙齒矯正移動的效應，而牙齒矯正移動也並未加重關節炎在血清中發炎因子濃度以及腦部神經發炎的程度。 | zh_TW |
| dc.description.abstract | Inflammatory molecules, various cytokines, chemokines, and MMPs are all involved in regulating systemic inflammatory diseases such as rheumatoid arthritis and local inflammatory responses such as orthodontic tooth movement. Therefore, this study aimed to investigate the interaction and association between "systemic inflammatory diseases" and "locally induced inflammatory responses."
In our study, collagen-induced arthritis (CIA) and/or orthodontic tooth movement (OTM) were induced in a previously established Mmp-3 promoter-Luciferase-emGfp transgenic rat model. Luciferase signal from Mmp-3 promoter was monitored by non-invasive in vivo imaging system (IVIS), concentration of various cytokines and chemokines in serum were detected, and the distance of tooth movement was measured using micro-CT imaging. Finally, specimen slices and immunofluorescence staining were used to observe the expression of neuroinflammatory markers such as MMP-3, Iba-1, and GFAP in the cerebral cortex and hippocampus. The experimental results showed that the luciferase signal in the molar area of all groups significantly increased on the first day after placement of the orthodontic appliance, but there was no significant difference between the CIA group and the CIA combined OTM group. The inflammatory factor concentrations in serum of both CIA group and CIA combined OTM group showed a bimodal distribution, but the amount of increase in the second peak of the combined group showed no significant difference with the CIA group. The immunofluorescent signals of anti-MMP-3, Iba-1 or GFAP in the cerebral cortex and hippocampus of CIA group and combined group were greater than those in the normal saline (N/S) control group, but there was no statistically significant difference between the CIA group and the combined group. This study suggests that systemic inflammation does not affect the rate of orthodontic tooth movement or induction of Mmp-3 promoter at local area, and regional orthodontic tooth movement does not exacerbate the concentration of inflammation factors in serum or degrees of neuroinflammation in arthritis either. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-05-19T08:56:11Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2023-05-19T08:56:11Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 ii Abstract iii 目錄 v 附圖目錄 ix 第一章 引言 1 1.1 類風濕性關節炎 1 1.1.1類風濕性關節炎與相關的細胞激素和趨化因子 1 1.1.2 類風濕性關節炎與MMP-3 2 1.2 牙齒矯正移動 4 1.2.1 牙齒矯正移動與相關的細胞激素和趨化因子 4 1.2.2 牙齒矯正移動與MMP-3 5 第二章 實驗目的 7 第三章 研究方法 8 3.1 動物模型 8 3.1.1 基因轉殖大鼠與麻醉及犧牲方式 8 3.1.2 膠原蛋白誘發關節炎大鼠模型 8 3.1.2.1 配製乳狀液 8 3.1.2.2 實驗組與對照組 9 3.1.2.3 誘發關節炎之測量與判定 9 3.1.3 牙齒矯正移動模型 10 3.1.3.1 矯正裝置的裝設 10 3.1.3.2 實驗組與對照組 10 3.1.4 合併膠原蛋白誘發關節炎與牙齒矯正移動模型 11 3.2 MMP-3 的偵測 11 3.2.1 MMP-3偵測與量化的方式 11 3.2.2 偵測 MMP-3 的時間點 12 3.3 血清檢驗 12 3.3.1 採血方式 12 3.3.2 採血時間點 13 3.3.3 Multiplex分析 13 3.4 測量牙齒矯正移動距離 14 3.4.1 微電腦斷層 (Micro-CT) 影像 14 3.4.2 Micro-CT影像定位 (Orientation) 14 3.4.3 牙齒移動距離之測量方式 14 3.5 石蠟切片製作及免疫螢光染色 14 3.6 統計方法 15 第四章 實驗結果 16 4.1 誘發關節炎判定結果 16 4.1.1 後肢重量及腳掌厚度變化 16 4.1.2 關節炎程度評分 16 4.2 牙齒矯正移動結果 16 4.3 非侵入式活體光學影像系統拍攝影像結果 17 4.3.1 牙齒矯正移動與MMP-3之表現 17 4.3.2 膠原蛋白誘發關節炎與MMP-3之表現 18 4.3.3 眼部MMP-3之表現 18 4.4 血清檢驗數值結果 19 4.4.1 牙齒矯正移動與血清內細胞激素和趨化因子濃度變化 19 4.4.2 關節炎與關節炎合併牙齒矯正移動之血清內細胞激素和趨化因子濃度變化 20 4.5 免疫螢光染色結果 20 4.5.1 牙齒矯正移動的影響 20 4.5.1.1 MMP-3在大腦皮質及海馬迴的訊號 20 4.5.1.2 Iba-1在大腦皮質及海馬迴的訊號 21 4.5.1.3 GFAP在大腦皮質及海馬迴的訊號 21 4.5.2有無合併牙齒矯正移動對膠原蛋白誘發關節炎的影響 22 4.5.2.1 MMP-3在大腦皮質及海馬迴的訊號 22 4.5.2.2 Iba-1在大腦皮質及海馬迴的訊號 22 4.5.2.3 GFAP在大腦皮質及海馬迴的訊號 23 第五章 討論 24 5.1 實驗設計 24 5.1.1 動物模型 24 5.1.2 誘發關節炎的方式及結果 24 5.1.3 實驗組與對照組的設計 25 5.2利用IVIS觀察MMP-3之訊號 25 5.2.1口腔部位的MMP-3訊號 25 5.2.2 關節部位的MMP-3訊號 26 5.2.3 眼部的MMP-3訊號 27 5.3 利用血清檢驗觀察Cytokines和Chemokines濃度變化 27 5.3.1 矯正裝置的影響 27 5.3.2 矯正裝置對關節炎的影響 28 5.3.3 組內差異的原因 29 5.4 免疫螢光染色觀察腦部變化 29 5.4.1免疫螢光染色的目標選擇 29 5.4.2 矯正裝置對關節炎腦部的影響 30 5.4.3 矯正裝置對腦部的影響 31 5.4.4 組內差異的原因 31 第六章 結論 33 第七章 未來研究方向 34 附圖 35 參考文獻 73 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 海馬迴 | zh_TW |
| dc.subject | 多重蛋白質與核酸標的偵測 | zh_TW |
| dc.subject | 基質蛋白金屬酶 | zh_TW |
| dc.subject | 膠原蛋白誘發關節炎 | zh_TW |
| dc.subject | 牙齒矯正移動 | zh_TW |
| dc.subject | 非侵入式活體光學影像系統 | zh_TW |
| dc.subject | orthodontic tooth movement | en |
| dc.subject | in vivo imaging system | en |
| dc.subject | multiplex immunoassays | en |
| dc.subject | matrix metalloproteinase | en |
| dc.subject | collagen-induced arthritis | en |
| dc.subject | hippocampus | en |
| dc.title | 由Mmp-3啟動子之基因轉殖大鼠研究牙齒矯正移動與關節炎之交互關係 | zh_TW |
| dc.title | Interaction of Orthodontic Tooth Movement and Arthritis by Using Mmp-3 Promoter Transgenic Rats | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 王詩凱;林君榮 | zh_TW |
| dc.contributor.oralexamcommittee | Shih-Kai Wang;Chun-Jung Lin | en |
| dc.subject.keyword | 膠原蛋白誘發關節炎,牙齒矯正移動,基質蛋白金屬酶,非侵入式活體光學影像系統,多重蛋白質與核酸標的偵測,海馬迴, | zh_TW |
| dc.subject.keyword | collagen-induced arthritis,orthodontic tooth movement,matrix metalloproteinase,in vivo imaging system,multiplex immunoassays,hippocampus, | en |
| dc.relation.page | 77 | - |
| dc.identifier.doi | 10.6342/NTU202300771 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2023-05-09 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 臨床牙醫學研究所 | - |
| 顯示於系所單位： | 臨床牙醫學研究所 | |
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