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研究生:張凰真
研究生(外文):Huang-Chen Chang
論文名稱:類風濕性關節炎病人的關節液與滑膜組織的細胞激素表現
論文名稱(外文):The cytokine profile in synovial tissue and synovial fluids from patients with rheumatoid arthritis
指導教授:林季千
指導教授(外文):Cheng-Chieh Lin
口試委員:陳得源黃春明
口試日期:2011-07-26
學位類別:碩士
校院名稱:國立中興大學
系所名稱:生命科學院碩士在職專班
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2011
畢業學年度:99
語文別:中文
論文頁數:45
中文關鍵詞:細胞激素類風濕性關節炎
外文關鍵詞:CytokineRheumatoid arthritis
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類風濕性關節炎(rheumatoid arthritis; RA)屬於一種慢性發炎疾病,罹患率佔全球總人口數的百分之一。RA會引起關節液增多,白血球浸潤及關節變形等發炎反應。細胞激素於發炎過程中扮演極重要的角色,可促使發炎反應更加嚴重並造成關節的損傷。本研究利用酵素連結免疫分析法(enzyme-linked immunosorbent assay),偵測RA、骨關節炎(osteoarthritis;OA)及紅斑性狼瘡(SLE)患者中,血清與關節液中IL-1β,TNF-α,IL-6,IL-17,IL-22,IFN-γ含量。結果發現類風濕性關節炎血清中的IL-1β,TNF-α表現量明顯高於骨性關節炎(p<0.0001)、紅斑性狼瘡(p<.0.0005)和正常人(p<0.0001)。在IL-6的表現中,RA與SLE明顯高於OA與正常人(P<0.01),但在RA與SLE彼此間無統計上差異。在IL-17中,各個組別在彼此間皆無統計上差異。而在關節液中RA比OA可偵測到高含量的IL-1β(<0.05)和TNF-α(<0.01)。且關節液中的IL-6值高於血清中的值,P<0.005。另外利用即時聚合酶連鎖反應(Real-time Polymerase Chain Reaction)分析類風濕性關節炎、骨性關節炎病人組織IL-6與TNF-αmRNA量的表現,結果發現在RA中,會有較高的IL-6與TNF-α表現。綜合以上的研究結果顯示,類風濕性關節炎是一種以關節為主的慢性全身性發炎疾病,而細胞激素IL-1β,TNF-α,IL-6與RA患者的疾病的發展有密切的關係。

Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly targets the synovial membrane, cartilage and bone. It affects 1% of the population and is associated with significant morbidity and increased mortality.Cytokines are directly implicated in many of the immune processes that are associated with the pathogenesis of RA. In this study, we measured the sera and synovial fluids cytokine levels including IL-1β, TNF-α, IL-6, IL-17, IL-22 and IFN-γ by enzyme-linked immunosorbent assay (ELISA) from patients with RA, osteoarthritis (OA) and systemic lupus erythematosus (SLE).
We demonstrated that RA patients expressed significantly higher levels of IL-1β and TNF-α in sera than OA (p&lt;0.0001), SLE (p&lt;0.0005) and healthy control(HC) (p&lt;0.0001). Sera levels of IL-6 in RA and SLE patients significantly higher than in OA and HC (P &lt;0.01), There are no differences in sera levels of IL-6 between RA patients and SLE patients. There are no statistical differences in the sera levels of IL-17 between RA patients and OA patients. In synovial fluids, RA patients expressed significantly higher levels of IL-1β(p&lt;0.05) and TNF-α(p&lt;0.01) than OA .Besides, we analyzed IL-6, TNF-alpha gene expression in synovial tissues from RA and OA paients by Real time PCR (Real-time Polymerase Chain Reaction). We demonstrated increased expression of TNF-αand IL-6 expression in RA synovial samples compared with osteoarthritis synovium.
In conclusion, IL-1β, TNF-α and IL-6 were highly expressed in sera, synovial fluids and synovial tissue in RA patients as compared with OA. Our data indicated that proinflammatory cytokines such as IL-1β, TNF-α, IL-6 may regulate inflammatory processes that were implicated in the pathogenesis of rheumatoid arthritis.



目錄

致謝………………………………………………………………………i
中文摘要…………………………………………………………………ii
英文摘要…………………………………………………………………iii
目錄………………………………………………………………………v
圖表目錄…………………………………………………………………vii
第一章、序論……………………………………………………………1
一、關節炎………………………………………………………………1
二、細胞激素……………………………………………………………8
三、類風濕性關節炎與骨關節炎對關節軟骨的損傷…………………11
四、研究目的……………………………………………………………12
五、實驗設計……………………………………………………………12
第二章、材料與方法……………………………………………………14
一、檢體採集……………………………………………………………14
二、檢體前處理…………………………………………………………14
三、實驗方法……………………………………………………………16
四、統計分析……………………………………………………………20
第三章、研究結果………………………………………………………22
一、病人性別與年齡分布………………………………………………22
二、細胞激素在血液與關節液中的表現………………………………22
三、關節組織中細胞激素的表現………………………………………24
四、類風濕性關節炎病人活動期與細胞激素關係……………………25
五、細胞激素相關性分析………………………………………………25
第四章、討論……………………………………………………………27
第五章、參考文獻………………………………………………………32

圖表目錄

表一、血清與關節液之細胞激素在不同關節炎中之表現量…………37
表二、類風濕性關節炎病人活動期與細胞激素關係…………………38
表三、類風濕性關節炎血清中發炎前趨性細胞激素相關性分析……39
表四、骨性關節炎血清中發炎前趨性細胞激素相關性分析…………40
表五、紅斑性狼瘡血清中發炎前趨性細胞激素相關性分析…………41
表六、類風濕性關節炎關節液中發炎前趨性細胞激素相關性分析…42
圖一、關節炎病人中,血清中細胞激素表現量比較…………………43
圖二、關節炎病人中,關節液中細胞激素表現量比較………………44
圖三、關節炎病人中,組織檢體中mRNA IL-6與TNF-α表現量比較…45

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