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研究生:施玫如
研究生(外文):Mei-Ju Shih
論文名稱:研究繆勒氏肌於甲狀腺眼瞼攣縮之致病角色
論文名稱(外文):The Role of the Müller Muscle in the Pathogenesis of Thyroid Lid Retraction
指導教授:莊立民莊立民引用關係
指導教授(外文):Lee-Ming Chuang
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:2004
畢業學年度:92
語文別:中文
論文頁數:64
中文關鍵詞:眼瞼攣縮免疫組織化學染色甲狀腺眼疾繆勒氏肌葛瑞芙氏眼病變
外文關鍵詞:immunohistochemistrythyroid eye diseaselid retractionMueller muscle
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背景:葛瑞芙氏症或稱為突眼性甲狀腺腫病、此群病人除了表現甲狀腺弁鄐振i症狀外、約25-50%的病人會有眼部方面的問題,特稱為甲狀腺眼病變。目前認為葛瑞芙氏症屬於自體免疫疾病、而主要之自體抗原可能為甲促素受體。目前尚不清楚甲狀腺眼病變的致病原因、但由於兩者發生時間有其相關性,認為其亦是自體免疫疾病。甲狀腺眼病變之臨床表現型分為凸眼、軟組織水腫、斜視、眼瞼攣縮及壓迫性視神經病變五大類,其中上眼瞼攣縮為最常見的表現型。目前較多之研究集中於造成凸眼之眼窩結締組織及眼外肌兩方面,釵h相關研究已證明眼窩及眼外肌周圍之纖維母細胞扮演重要之中樞角色、其可在釵h生長因子或細胞介素刺激下,分泌葡萄醣胺類造成組織水腫、另外其亦可分化為脂肪細胞造成眼窩脂肪組織增加。然而回顧遏去的文獻、對於上眼瞼攣縮的研究卻頗為缺乏,不僅對於繆勒氏肌可能引起之致病機轉眾說紛紜、且於病理層面的分析亦缺乏一致性之結果;導致上眼瞼攣縮這部分的研究進展緩慢,推究原因在於病理方面的評估或實驗方法不夠客觀。鑑於此、我們提出利用影像分析軟體合成及計算繆勒氏肌中之病理組成、並配合臨床因子做相關性分析,以釐清繆勒氏肌於上眼瞼攣縮所扮演的角色。
方法:臨床方面-病例組方面:以回溯方法收集甲狀腺眼病變病人須矯正上眼瞼攣縮之基本資料:包括性別、年齡、發病時間、甲狀腺弁鄎�數狀態、甲促素受體之抗體狀態、藥物、抽菸史及家族史。評估並記錄上眼瞼攣縮程度及眼球凸度。病理方面-收集具甲狀腺上眼瞼攣縮、其甲狀腺弁鄎�數正常及攣縮程度穩定病人之繆勒氏肌為病例組、另取不具甲狀腺疾病史但須矯正眼瞼下垂病人之繆勒氏肌為對照組。取下之兩組檢體均以福馬林固定及石蠟包埋、並依序染蘇木紫及伊紅之常規染色、甲苯胺藍法、Masson氏三色特殊染色法以區分肌肉及纖維化組織。並接著做多項免疫組織化學染色:包括LCA、CD3、CD20、CD68、HLA-DR、Caspase 3及TSHr。為了增加影像分析的客觀性、選擇利用Adobe Photoshop version 7.0.1組合影像並量化繆勒氏肌中之病理組成。而量化組織學及免疫組織化學法、則採計算20個400倍高倍率顯微鏡下,累加免疫發炎細胞及具陽性免疫染色細胞之總數做指標。
結果:臨床方面-共收集三十一個病例組及七個正常組之繆勒氏肌。病人的平均年齡39.13±9.40歲、平均開刀前之上眼瞼攣縮平均值為7.58±0.81釐米、術前之平均凸度為19.68±2.56釐米、分析的病人群中約10%之甲狀腺弁鄎�數為正常、血中對抗甲促素受體之抗體陽性率為68.4%、內科治療方式方面仍以服用抗甲狀腺藥物為主、12.9% 有抽菸史、9.7% 具甲狀腺疾病之家族史。利用相關之分析,發現當病人年齡愈大 (r=0.407, p=0.023)、發生甲狀腺弁鄐振i之時間愈長(r=0.501, p=0.004)及甲狀腺弁鄎�數偏高�?(p=0.045),上眼瞼攣縮之程度亦愈嚴重。病理方面-以Photoshop影像軟體合成及分析、發現病例及正常組間之繆勒氏肌之病理組成有明顯不同,於病例組之繆勒氏肌中有明顯的脂肪增生(P=0.032)、纖維化增加(P=0.006)及肌肉纖維減少(P<0.001)。於上眼瞼攣縮較嚴重的族群中、纖維化之程度亦較明顯。正常人之繆勒氏肌中、存有肥大細胞及巨噬細胞,然而於病例組中巨噬細胞數目有明顯增加(P=0.004),相反地,巨大細胞之數目則明顯減少(P<0.001)。而巨噬細胞數目則又與繆勒氏肌中之纖維化組織含量及眼瞼攣縮之嚴重度有關。兩組繆勒氏肌中、均沒有B淋巴球的存在、T淋巴球亦僅佔少數、也沒有細胞表現TSHr及HLA-DR。另外我們亦證實、於病例組中繆勒氏肌的肌肉纖維之減少與細胞凋亡可能無關。
結語:於臨床資料之分析、發現上眼瞼攣縮程度與年齡、發病時間長短、甲狀腺弁鄎�數狀態具相關性。於病理組織之分析、發現甲狀腺眼病變病人之繆勒氏肌確實與正常繆勒氏肌不同、且其纖維化程度與攣縮較嚴重者具顯著之相關性,此可佐證繆勒氏肌之纖維化可能是造成上眼瞼攣縮的致病原因,且可證明繆勒氏肌也是甲狀腺眼病變中自體免疫反應作用的另一個標的組織。而繆勒氏肌之纖維化與巨噬細胞有關,此發現可提供研究甲狀腺眼病變尤其是上眼瞼攣縮部分、於細胞層面的重要訊息。於病例組中、以免疫組織化學染色法無法證實TSHr 之存在,未來有待進一步釐清是否因含量微少不易偵測、亦或是TSHr並非繆勒氏肌之主要抗原。
目錄
致謝 I
目錄 II~III
縮寫表…………………………………IV

一、中文摘要………………………………5
二、緒論……………………………………8
(一)、研究背景與文獻回顧………………8
(二)、研究之動機及目的…………………13
(三)、研究的假說…………………………13
三、 研究方法與材料………………………15
四、 結果……………………………………19
五、 討論……………………………………23
六、 展望……………………………………27
七、 論文英文簡述…………………………30
八、 參考文獻………………………………38
九、 圖表……………………………………45
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