物理性刺激與藥物複合治療股骨頭壞死動物之研究

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Title:	物理性刺激與藥物複合治療股骨頭壞死動物之研究 Studies on the therapeutic effect of physical stimulation combined with Alendronate on animal model with femoral head osteonecrosis
Authors:	何婷婷
Contributors:	生物科技系暨研究所李國榮賴國安
Keywords:	福善美單一脈衝式電磁場股骨頭壞死類固醇 Osteonecrosis of the femoral head Corticosteroid single pulsed electromagnetic field Alendronate
Date:	2012
Issue Date:	2012-11-29 11:36:21 (UTC+8)
Abstract:	隨著醫療進步，我們知道類固醇廣泛應用於疾病上治療，如內分泌疾病、風濕性疾病、皮膚疾病、過敏疾病等，而類固醇的使用也是造成非創傷性股骨頭壞死的危險因素之一。儘管類固醇在臨床治療上有極大貢獻，卻使得患者可能有罹患股骨頭壞死的風險，不過目前類固醇誘導骨壞死的機制尚未明確。在台灣此疾病常發生於45-65歲中壯年人口(1)，而這個族群為家庭主要的經濟來源。股骨頭壞死初期無症狀易被忽略，如果不及時治療，有超過 70 % 股骨頭壞死的患者將導致髖關節破壞與股骨頭崩塌，最後終將走向人工髖關節置換的命運，由於股骨頭壞死的發生會造成生活上不便利性，故在治療崩塌前的預防即為重要的課題(2)。本研究目的為使用股骨頭壞死動物模型建立探討單一脈衝式電磁場、福善美 (alendronate) 應用於類固醇誘發股骨頭壞死骨質改變之效應，進行新療法開發，期望可就由此研究找到股骨頭崩塌前的治療。材料方法本實驗使用 70 隻 12 週大白鼠隨機分派 7 組，分為對照組、負控制組、正控制組、單一脈衝式電磁場組 (包括高頻率單一脈衝式電磁場與低頻率單一脈衝式電磁場) 及合併治療組 (包括高頻率單一脈衝式電磁場合併 alendronate 與低頻率單一脈衝式電磁場合併 alendronate。每兩天注射糖皮質類固醇 (40 mg/kg methylprednisolone) 及 4 週負重訓練誘導股骨頭壞死隻動物模型，之後分別應用單一脈衝式電磁場及單一脈衝式電磁場合併 alendronate 治療兩種方式做 6 週治療，分別命名為單一脈衝式電磁場組及合併治療組。結果首先由外觀觀察，在各組皆未有崩塌的變化。再利用微電腦斷層 (Micro-CT) 及蘇木紫-伊紅染色 (H & E stain) 獲取股骨頭骨骺之骨形態學與組織學參數。由組織學切片結果顯示：藉由類固醇注射及負重訓練的方式大白鼠之骨骺處脂肪細胞有明顯體積增大與數量增加的趨勢，但沒有骨細胞死亡之組織學特徵，而在高頻率單一脈衝式電磁場刺激卻有破壞骨細胞的現象。由微電腦斷層 (Micro-CT) 結果顯示：使用 One-way ANOVA 進行 7 組 22 週犧牲之大鼠股骨骨骺 (epiphysis) 分析比較負控制組、正控制組、高頻率單一脈衝式電磁場組、低頻率單一脈衝式電磁場組骨骺 (epiphysis) 之骨體積百分比、骨小樑厚度及骨小樑數量有相似的數值且沒有顯著差異。負控制組、正控制組、高頻率單一脈衝式電磁場組、低頻率單一脈衝式電磁場組骨骺 (epiphysis) 之骨體積百分比及骨小樑厚度高於對照組，但骨小樑數量卻低於對照組；合併治療組骨骺 (epiphysis) 之骨體積百分比及骨小樑厚度高於其他組別，但骨骺 (epiphysis) 之骨小樑數量卻低於其他組別。結論本研究結果推估在本實驗中單獨以單一脈衝式電磁場作治療對骨骺 (epiphysis) 的骨質沒有太大的影響，所以在骨體積百分比、骨小樑厚度及骨小樑數量沒有太大的改變，但可降低骨小樑間隙；而在合併福善美 (alendronate) 對骨骺 (epiphysis) 有較大的骨質影響，可提高骨體積百分比、骨小樑厚度，亦可降低骨小樑間隙。 With the medical advances, corticosteroid is widely used in the treatment of many diseases (ie. Endocrine Disorders、Rheumatic Disorders、Dermatologic Diseases、Allergic States), which is the most common non-traumatic cause of osteonecrosis of the femoral head. In clinical, the corticosteroid treatment has most contributions, but patients also exposed to the risk of osteonecrosis. Despite the strong association of glucocorticoids with osteonecrosis of the femoral head, but the underlying mechanisms have been unclear. In Taiwan, the illness largely affects male population, especially the age in forty-five to sixty-four(1). It is initially asymptomatic, and if left untreated, more than 70 % of instances of osteonecrosis of the femoral head lead to collapse of the femoral head with subsequent hip joint destruction. Most cases advance to secondary osteoarthritis (OA), and the patient eventually requires total hip arthroplasty (THA). Therefore, early intervention before collapse would be a better strategy for treatment(2). The purpose of this study is using single pulsed electromagnetic field (SPEMF) and Alendronate on steroid-induced osteonecrosis femoral head of S.D. rats animal model. To hope finding a new therapeutic to treatment femoral head osteonecrosis. Materials and Methods: 12-weeks-old S.D. rats were randomly assigned seven groups including control group (A), negative control group (B), positive control group (C), HF-SPEMF group (D), LF-SPEMF group (E), HF-SPEMF + ALN group (F) and LF-SPEMF + ALN group (G). 70 rats was injection of 40 mg/kg methylprednisolone every other day for two weeks and treadmill for four weeks. The rats were treatment using SPEMF and SPEMF combined with Alendronate for six weeks after the establishment of animal model with femoral head osteonecrosis. Ruselt After the rats were sacrificed, and femoral head were took out. The morphology were observed normal of each groups. Using H & E stain to observe epiphysis of the femoral head. The result were observed bone morrow, the rats injection steroids and treadmill training has hypertrophy and hyperplasia of fat cells on epiphysis, and most groups of the osteocyte was still alive, but in HF-SPEMF group, which osteocyte was death. Using Micro-CT scanning to analysis percent of bone volume, trabecular thickness, trabecular separation, and trabecular number and compare of seven groups using ANOVA analysis. The results of that negative control group, positive control group, HF-SPEMF group and LF-SPEMF group has similar and non-significant in percent of bone volume, trabecular thickness and trabecular number,. In the percent of bone volume and trabecular thickness, negative control group, positive control group, HF-SPEMF group and LF-SPEMF group was higher than control group, but the trabecular number opposite. In the percent of bone volume and trabecular thickness, HF-SPEMF + ALN group and LF-SPEMF + ALN group was higher than each groups, but the trabecular number opposite. Conclusion In this study estimate that using only SPEMF therapy was no effect in percent of bone volume, trabecular thickness and trabecular number on epophysis, but decrease trabecular separation. Combined with Alendronate make percent of bone volume, trabecular thickness and decrease trabecular separation.
Relation:	校內校外均不公開，學年度：100，106頁
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Dissertations and Theses

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