中文摘要 背景 肌腱之細胞外間質包含了多種蛋白質及多醣類，它們除由局部之細胞分泌聚合成網狀結構外，並與細胞表面及其細胞外間質相互之間具有相互影響之功能。肌腱主要的細胞外間質有兩種： 一為葡萄糖胺聚合醣(glycosaminoglycans)，它與蛋白質共價聯結成蛋白多醣(proteoglycans)的形式；另一為纖維蛋白質，其依功能包括結構型蛋白（例如膠原蛋白<collagen>及彈性素<elastin>）及黏結型蛋白（例如纖維結合素<fibronectin>及板素<laminin>）。葡萄糖胺聚合醣及蛋白多醣在結締組織中會形成一種多水凝膠物質，它們因此而可抵抗肌腱外來之壓迫應力(compression force)；相對地膠原纖維，尤其是其分子內及分子間之交叉聯結體更提供了肌腱抵抗外來之牽拉應力(tension force)，而肩部旋轉肌腱之環境必須同時承受此二種應力。 肩部旋轉肌病變是產生肩關節疼痛及功能不良的一個主要來源，它常好發於40歲以上的成年及老年人，意含著正常的老化過程或許扮演著病變一個重要角色；然而它也常發生於有明顯外傷或常作舉肩運動或活動的年輕人， 正意味著或許是能對抗著壓迫及牽拉應力的細胞外間質發生改變而導致病變. 因為旋轉肌在是肩部一個包圍骨頭的特殊結構， 所以研究此一特殊解剖位置的肌腱內之細胞外間質成分的改變將有助於旋轉肌病變成因的瞭解。我們的假設是隨著年齡的增長，細胞外間質內對抗壓迫及牽拉應力的成分將有所改變，研究成果將有助於探究此一特殊地區之肌腱病變成因， 進而為將來利用分子生物學技術來預防其肌腱病變之發生而探路。 方法與材料 本實驗計劃將研究老鼠旋轉肌腱細胞外間質隨老化過程，成分的改變情形；運用組織化學，免疫組織化學之技術來定位1.葡萄糖胺聚合醣，2.蛋白多醣，3.膠原蛋白，及4.纖維結合素。將S-D大白鼠依年齡分成5組，每組10隻；分別為3週，3個月，6個月，9個月，12個月，用二氧化碳麻醉昏迷後，取出肩部旋轉肌腱加以切片、染色，光學顯微鏡觀察。 結果 我們得到的結果發現隨著年齡增長，肌腱排列較為緻密，細胞外間質對抗壓力的葡萄糖氨聚合醣(glycosaminoglycans,GAG)及對抗張力的膠原蛋白(Collagen)均在第三個月到第六個月這時期有明顯增加，之後呈現成熟穩定；而在第12個月時，纖維結合素(fibronectin)和肌腱旁絲纖維其表現則有漸漸明顯趨勢，出現退化的徵象。 結論 旋轉肌腱病變的研究隨生物化學及分子生物技術的改善，的確開啟新的領域，以實驗動物模型作為旋轉肌腱病變之研究可以與人類肌腱疾病有相似之比較；大白鼠旋轉肌腱隨年齡增加從幼年至成熟，其細胞外間質中對抗壓力及張力之葡萄糖氨聚合醣與膠原蛋白均有增加，表示肌腱的強度由年輕隨年齡漸大漸增強；當肌腱漸退化時（約第12個月），可見肌腱周邊有較多毛樣的纖維，但是細胞外間質的成份在第12個月時的表現未明顯減少；在第9-12個月可能細胞外間質成份的功能退化而未減少。我們必須延長實驗動物年齡來加以確認，; 英文摘要 Introduction : Rotator cuff pathology is a significant source of shoulder pain and dysfunction .Rotator cuff develops at the location where tendons wrap around bone and are subjected to transverse compressive loading ,in addition to longitudinal tension. The macromolecular composition characteristics of extracelluar matrix of the tendon in this region is crucial to identify the pathology. Our hypothesis is that the macromolecular compositions of extracellualr matrix related to compression and tensile stress of rotator cuff tendon are changed with age. Materials and methods: A total of 50 healthy male rats of Spraque-Dawley strains are used. They are divided into 5 groups according to their age: 3-week, 3- month, 6-month, 9-month, 12-month. The animals are sacrificed with CO2 narcosis. The upper limbs are extraarticulated at the scapulothoracic joint and the skin is removed .The limbs are kept at 24 hrs in 2 % glutaraldehyde buffered with cacodylate at PH7.4. The rotator cuff tendon is removed and postfixs for additional 48 hrs . Finally, the tendons are cut longitudinally and transversely. Histochemical analysis (localization of GAG :glycosaminoglycans; PG:proteoglycans) and immunohistochemical analysis (localization for collagen and fibronectin) were performed. Results: We find that the localization of collagen seem to be very identical with that of the GAG . Tendon fiber arrangement is getting more condensed with increasing age. The collagen and the GAG are both increased at the period form 3 months of age to 6 months of age. Both of them are stable and mature after 6 months of age .The fibronectin become more predominant at 12 months of age . Conclusion: .The macromolecular compositions of rotator cuff tendon in S-D rats increased with age. It indicated that the tendon can resist more tensile and compression stress with increasing age. When tendon is getting degenerated, the fibrillation around the tendon seemed to be predominant at 12 months of age.
