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標題: | 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 Interaction of Orthodontic Tooth Movement and Arthritis by Using Mmp-3 Promoter Transgenic Rats |
作者: | 林奕安 Yi-An Lin |
指導教授: | 姚宗珍 Chung-Chen Yao |
關鍵字: | 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, collagen-induced arthritis,orthodontic tooth movement,matrix metalloproteinase,in vivo imaging system,multiplex immunoassays,hippocampus, |
出版年 : | 2023 |
學位: | 碩士 |
摘要: | 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。 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/87411 |
DOI: | 10.6342/NTU202300771 |
全文授權: | 未授權 |
顯示於系所單位: | 臨床牙醫學研究所 |
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