臺灣博碩士論文加值系統

股骨頭壞死（缺血性股骨頭壞死，無菌性股骨頭壞死）是台灣人工髖關節手術最主要的疾病，這種疾病好發於30-40歲的年輕男性病患，不幸的是他們通常是家庭經濟的主要來源。治療方法的選擇與其嚴重的程度與壞死區域的大小有關，在崩塌前搶救股骨頭是最主要的目標。動物股骨頭壞死的模型可以用來研究病理機轉及臨床治療的方法。雙磷酸鹽製劑在動物實驗及臨床治療已有報告可延緩股骨頭壞死之崩塌。股骨頭壞死所引起的崩塌現象已可在兩足動物如鴯苗產生，但鴯苗在飼養成本上是非常昂貴的，所以在本實驗中我們利用SD大鼠（Sprague-Dawley rats），以高劑量類固醇誘導股骨頭壞死並以跑步機負重來模擬二足動物股骨頭受力的模式。
材料與方法
本實驗採用300-350公克人工飼養SD大鼠，將它們分成4組，A組12隻，每隻每兩天腹腔注射舒汝美卓佑（methylprednisolone 40mg/kg）。B組8隻，每隻每兩天腹腔注射生理食鹽水1ml（normal saline 0.9％NaCl）。C組8隻沒有投予任何藥物。D組8隻，注射與A組相同劑量之舒汝美卓佑，然後將A組、B組、C組在第3週到第6週每天在跑步機上（轉數：8-10rpm，斜度為18°）做跑步訓練10~15分鐘，但D組並未做任何跑步訓練。
在研究初期將這些大鼠每2週做一次股骨頭X光照相，這些老鼠在第7週及第8週犧牲掉，將股骨取出做微電腦斷成掃描及病理組織切片的研究，測量股骨軟骨與長骨體生長部（physis）的距離來判定股骨頭畸形程度。最後利用Student 氏 t-檢定及ANOVA來比較各群組的差別。
結果
A組在實驗中有兩隻大鼠死亡，在第6週A組存活大鼠中有17支股骨頭有變形現象（85％），但B組、C組及D組並未發現股骨頭變形現象。巨觀檢視，發現在A組大鼠股骨頭有17支明顯變形的現象（85％），在A組中股骨軟骨與長骨體生長部平均值為1.2616與B、C、D各組比較股骨有明顯變薄的現象，B組平均值為1.383，P值＜0.001；C組平均值為1.4，P值＜0.001；D組平均值為1.389，P值＜0.001。
意義及結論
在SD大鼠的實驗中我們利用高劑量類固醇及跑步機負重訓練，建立一種動物股骨頭壞死的模式，對這種體型較小的四足動物股骨頭崩塌及變形的現象，可以用藥物及負重訓練的方式誘導產生，這種動物模型的建立可以模擬兩隻腳走路的人類股骨頭壞死的模式，這種模式的實驗花費較少，實驗做起來比兩隻腳的較為簡單，並且能進一步用來做研究股骨頭壞死治療的模式。

Osteonecrosis (Avascular necrosis, Aseptic necrosis) of the femoral head is the most common illness that leads to artificial joint replacement in Taiwan. This illness largely affects young male population of the third and fourth decades, who usually are the major source of family income. Treatment options depend on the stage and percentage of the necrotic area. Salvage of the femoral head is the top priority before collapse. Animal models of femoral head necrosis were applied to study the pathological mechanism and trial therapy. Bisphosphonate compounds were applied in animal studies and clinical trials to reduce and delay deformity of the necrotic femoral head. However, collapse of the necrotic femoral head only could be produced in bipedal animals such as emu, which is expensive and difficult to raise. In this study, we propose a SD rat animal model. In this model, high-dose corticosteroid is used to induce osteonecrosis of the femoral head and treadmill running is applied to stress the femoral head mimicking a bipedal weight bearing of the femoral head.

Materials and Methods:
36 Spague-Dawley rats weighing 300-350 grams were raised. They were devided into four groups. Group A, 12 rats, each received intraperitoneal injection of 40mg/kg methylprednisolone every other day for two weeks. Group B, 8 rats, each received 1ml normal saline （0.9％NaCl）peritoneal injection every other day for 2 weeks. Group C, 8 rats, they received no injection. Group D, 8 rats, the injection was the same as that of the group A. Groups A, B and C rats underwent tread mill running(8-10 rpm, 18 degree upward slope) 10 to 15 minutes per day from the third to the sixth week. The group D rats did not underwent this treadmill running.
Roentgenograms of the femoral heads were taken at the beginning of study and every 2 weeks thereafter. The animals were sacrificed at 7 weeks and 8 weeks. The femur were retrieved for Micro-CT and histo-pathological study. Measurement of the distance between the articular cartilage to the physis was applied for an indication of femoral head deformity.
Student t test and ANOVA were applied to compare among the groups.

Results:
Two rats in the Group A died during the study. At the 6th week, roentgenogram showed deformity of 17 femoral heads in the survived Groups A rats 85％ while the deformity was not detectable in all the rats of Groups B、C and D. Gross inspection also found deformity in all the retrieved femoral heads in the group A rats. The distance between the articular cartilage to the physis averaged 1.2616 in Group A, which is significantly thinner than that of the Group B averaged 1.383, p＜0.001, Group C averaged 1.4, p＜0.001 and Group D averaged 1.389, p＜0.001.

Significance and conclusion:
By using high dose corticosteroid and treadmill running to SD rats, we established an animal model of femoral head necrosis. Collapse and deformity of the femoral head can be produced in this small four-footed animal model. This animal model mimics osteonecrosis of the femoral head in humane beings. This model is less expensive and easier to maintain than bipedal animals, and can be applied for further study of treatment modalities of osteonecrosis of the femoral head.

中文摘要..................................................I
英文摘要.................................................Ⅲ
本文目錄.................................................Ⅵ
縮寫表...................................................Ⅷ
表目錄...................................................Ⅸ
圖目錄...................................................Ⅹ
第一章 緒論..............................................1
1.1 前言.................................................1
1.2 股骨頭缺血性壞死的因素與分類.........................1
1.3 股骨頭缺血性壞死分期.................................5
1.4 股骨頭壞死治療方式及臨床處置.........................7
1.5 致病的機轉...........................................8
1.6 骨骼系統.............................................8
1.7 高解析度電腦斷層掃描儀...............................11
1.7.1 電腦斷層掃描儀原理..............................12
1.7.2 高解析度電腦斷層掃描儀應用.........................13
1.8 致股骨頭壞死崩塌之動物模式建立.......................14
1.9 研究動機與目的.......................................15
第二章 材料與方法........................................17
2.1 材料.................................................17
2.2 實驗方法.............................................18
第三章 結果..............................................22
3.1動物行為觀察..........................................22
3.2 X-光影像分析.........................................22
3.3股骨頭外觀觀察........................................23
3.4 Micro-CT分析.........................................24
3.5 組織病理分析.........................................24
第四章 討論..............................................26
第五章 結論..............................................31
參考文獻.................................................32
附表.....................................................38
附圖.....................................................41

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