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研究生:許詠瑞
研究生(外文):Yung-Ray Hsu
論文名稱:在大鼠之實驗性自體免疫前葡萄膜炎中microRNA之表現
論文名稱(外文):Expression of microRNAs in the Eyes of Lewis Rats with Experimental Autoimmune Anterior Uveitis
指導教授:楊長豪楊長豪引用關係
指導教授(外文):Chang-Hao Yang
口試委員:楊中美楊偉勛
口試委員(外文):Chung-May YangWei-Shiung Yang
口試日期:2015-07-17
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:英文
論文頁數:43
中文關鍵詞:免疫葡萄膜炎microRNA
外文關鍵詞:microRNAuveitisiritis
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實驗目的
研究NF-κB相關之microRNA以及細胞激素在大鼠之實驗性自體免疫前葡萄膜炎(EAAU) 之動態表現,並提出可能的免疫機轉分析。
實驗方法
本實驗以melanin-associated antigen在Lewis rat上誘發EAAU,並記錄臨床發炎程度以及前房液中白血球之數量。在進行虹膜、睫狀體、以及淋巴結之RNA萃取後,作者分析8個miRNA (miR-155-5p,miR-146a-5p,miR-182-5p,miR-183-5p,miR-147b,miR-21-5p,miR-9-3p,miR-223-3p)以及六個細胞激素(IFN-γ, IL-17, IL-12p35, IL-1β, IL-6, IL-10) 在病程中之動態變化。另外,為了確認上述實驗結果,也施作miRNA原位雜合以及ELISA以定量細胞激素。
結果
臨床發炎程度以及前房液中白血球之數量皆在疾病誘發後第15天達到高峰。miRNA分析發現miR-146a-5p、miR-155-5p、miR-223-3p、miR-147b在疾病中減弱表現,而miR-182-5p、miR-183-5p、及miR-9-3p則增強表現。細胞激素中,IFN-γ、IL-17、IL-12p35、IL-1β、及IL-6表現量上升,而IL-10表現則下降。
結論
miRNA的動態變化可能啟動NF-κB訊息傳遞,進而引發下游的Th17和Th1免疫細胞以及相關細胞激素之活化,以造成實驗性自體免疫前葡萄膜炎。

Purpose
To determine the dynamic changes of NF-κB-related microRNAs and cytokines in the course of experimental autoimmune anterior uveitis (EAAU) and elucidate the possible immunopathogenesis.
Materials and methods
Uveitis was induced in Lewis rats with bovine melanin-associated antigen. The clinical scoring of the inflammatory activity of the anterior chamber and leukocyte quantification in aqueous humor was done. RNA extraction from iris/ciliary body, and popliteal lymph nodes was performed to reveal the dynamic changes of 8 target miRNAs (miR-155-5p, miR-146a-5p, miR-182-5p, miR-183-5p, miR-147b, miR-21-5p, miR-9-3p, and miR-223-3p) and mRNAs of 6 cytokines (IFN-γ, IL-17, IL-12p35, IL-1β, IL-6, IL-10). miRNA in situ hybridization and ELISA quantification of cytokines were performed to confirm the results.
Results
The disease activity and leukocyte quantification was maximal on day 15 following immunization. miRNA profiling revealed down-regulation of miR-146a-5p, miR-155-5p, miR-223-3p and miR-147b, and up-regulation of miR-182-5p, miR-183-5p, and miR-9-3p. Cytokines analysis disclosed IFN-γ, IL-17, IL-12p35, IL-1β, and IL-6 over-expression with IL-10 down-regulation.
Conclusion
Dynamic changes of miRNAs were present in the EAAU course. By initiating NF-κB signaling, expressions of downstream cytokines and effector cells of Th17 and Th1 lineage were sequentially activated, and contributed to the disease.

口試委員會審定書………………………………………………………………..… i
序言及謝辭……………………………………………………………………….…. ii
中文摘要……………………………………………………………………………..iii
英文摘要……………………………………………………………………………..iv
緒論 (Introduction)…………………………………………………………………...1
研究方法與材料 (Materials and Methods) ………………………………………….4
結果 (Results) ………………………………………………………………………..9
討論 (Discussion) ………………………………………………………………...…12
參考文獻……………………………………………………………………………..20
表1…………………………………………………………………………….……..32
表2…………………………………………………………………………….……..33
圖1…………………………………………………………………………….……..34
圖2……………………………………………………………………………….…..35
圖3…………………………………………………………………………….….….36
圖4…………………………………………………………………………….….….37
圖5…………………………………………………………………………….….….38
圖6…………………………………………………………………………….….….39
圖7…………………………………………………………………………….….….41
圖8…………………………………………………………………………….….….42
附錄………………………………………………………………………….….……43


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