| 研究生: |
吳彥廷 Wu, Yen-Ting |
|---|---|
| 論文名稱: |
探討臨床肌腱病變過程與彈性蛋白酶之關聯 The Clinical Relevance of Elastase in pathogenesis of Tendinopathy |
| 指導教授: |
周一鳴
Jou, I-Ming |
| 學位類別: |
博士 Doctor |
| 系所名稱: |
醫學院 - 基礎醫學研究所 Institute of Basic Medical Sciences |
| 論文出版年: | 2016 |
| 畢業學年度: | 104 |
| 語文別: | 英文 |
| 論文頁數: | 86 |
| 中文關鍵詞: | 彈性蛋白酶 、彈性纖維 、肌腱病變 、膠原蛋白 |
| 外文關鍵詞: | Elastase, Elastic fiber, Tendinopathy, Collagen |
| 相關次數: | 點閱:116 下載:2 |
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急性或慢性的肌腱病變所造成的傷害在臨床上是骨科門診中常見的疾病之ㄧ,已知病患通常具有劇烈疼痛且復發率極高。目前臨床研究上對於肌腱病變所造成的原因仍不清楚。本研究透過研究臨床肌腱病變患者檢體,藉此臨床證據建立動物模型並探討其相關機制。首先,我們發現在人類的肌腱病變檢體中,其彈性蛋白的表現量明顯的降低,且彈性蛋白酶的表現量顯著增加。因此,我們假設彈性蛋白酶在肌腱病變過程中透過水解彈性蛋白造成肌腱病變。我們將彈性蛋白水解酶以超音波指引下注射入大鼠的阿基里斯肌腱外圍後發現,肌腱厚度在注射後21 天明顯增厚、運動功能42 天後明顯下降。在組織學的觀察下,細胞數量在注射後28 天明顯增加且型態改變。而彈性蛋白含量注射後14 天顯著降低伴隨著彈性蛋白酶顯著增加。注射後28 天,第一型膠原蛋白顯著降低及第三型膠原蛋白顯著增加。本研究發現在注射後28 天,此動物模型具備有與臨床肌腱病變相同
的多項主要特徵。此動物模式不但為本研究第一個發現並且建立在臨床證據之上,更避免掉以往動物模式費時或是穿刺肌腱的影響。既然彈性蛋白酶是肌腱病變過程中一個相關的因子,此項發現可能做為治療肌腱病變的可能基礎。
Acute tendonitis and chronic overuse tendinopathy comprise the majority of tendon injuries, and patients typically have severe pain and a high relapse rate. The intrinsic pathogenic mechanism underlying the development of tendinopathy is largely unknown. In this study, we investigated tendinopathy specimens from clinical patients and clinical evidence to establish an animal model and examine its possible mechanisms. The expression of elastin was decreased and elastase was increased in clinical human specimens. Therefore, we hypothesized that elastase-induced elastic fiber degradation led to the formation of tendinopathy. We used ultrasonography-guided peritendinous Achilles tendon injections of elastase for injection into rat limbs. Results showed that the thickness of the tendon increased during the 28 days of elastase injection, but tendon functionality decreased over 42 days after injection. In histological tendons, the number of cells increased during the 28-day period after injection, and the cell phenotype changed after injection. Expression of elastin was decreased and elastase increased during the 14-day period after injection. Collagen type I decreased and collagen type III increased during the 28-day period after injection. This novel animal model provided a high level of
reliability and reproducibility to create a type of tendinopathy that is similar to human chronic tendinopathy. Our model was avoided needle puncture injury and decrease experimental time. Because elastase played a critical role in the progression of tendinopathy in this study, the results may provide a potential treatment fortendinopathy in the future.
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