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研究生:張顧議
研究生(外文):Ku-I Chang
論文名稱:去卵巢骨鬆鼠使用發酵乳和雙磷酸鹽(alendronate)的協同骨保護作用研究
論文名稱(外文):A synergistic bone sparing effect of fermented milk andbisphosphonate(alendronate) in ovariectomized osteoporotic mice
指導教授:陳全木陳全木引用關係
口試委員:陳小玲杜旻育
口試日期:2016-07-18
學位類別:碩士
校院名稱:國立中興大學
系所名稱:生命科學院碩士在職專班
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:59
中文關鍵詞:骨質疏鬆症克弗爾雙磷酸鹽切除卵巢小鼠
外文關鍵詞:osteoporosisfermented milk (kefir)bisphosphonates (ALN)ovariectomized mice
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隨著老年人口的逐漸增加,骨質疏鬆症成為一個重要的健康問題。隨著歲月流逝,骨質將逐漸流失,而發生所謂的骨質疏鬆症(osteoporosis);當骨質流失後的骨骼受到外力衝擊時,便容易因結構支撐力不足而脆裂,因而發生骨折。文獻已證實單獨使用發酵乳克弗爾(kefir)或雙磷酸鹽(alendronate)對切除卵巢鼠有明顯改善骨質流失的成效。此研究將以發酵乳合併使用雙磷酸鹽治療切除卵巢小鼠之骨質流失對比於單獨使用發酵乳克弗爾或雙磷酸鹽之療效是否有協同加成的效果。本實驗室先前研究證實對去除卵巢的母鼠每日餵食克弗爾 12 週後可以有效改善因動情素缺乏所引起的骨質流失現象。為了降低長期使用ALN 的副作用以及評估克弗爾與 ALN組合治療的加成性效果,本研究以去卵巢小鼠為實驗模式,探討單獨低劑量ALN (10μg/kg)、單獨克弗爾(143 mg/kg) 和ALN+克弗爾組合治療在改善去卵巢小鼠骨鬆症狀上的差異。本實驗結果顯示合併使用ALN 與克弗爾可以顯著增加小鼠股骨皮質骨(cortical bone)的骨密度、樑狀骨(trabecular bone)體積和數目,顯著降低樑狀骨分散距離,並且有效延緩骨質流失。
With the gradual increase in the elderly population, osteoporosis has become an important health problem. With the passage of time, bone will gradually drain, and the occurrence of so-called 〝osteoporosis〞; when bone loss after the external impact of bone, it is easy due to lack of structural support and brittle fracture, and thus fracture. It has been confirmed that the use of fermented milk (kefir) or bisphosphonates (alendronate) alone has a significant effect in the improvement of bone loss on the ovariectomized rats. This study will combine the use of kefir and alendronate in the improvement of bone loss on the ovariectomized mice compared to the effect of using fermented milk or bisphosphonates alone. Previous studies have confirmed that the removal of ovariectomized rats daily 12 weeks after feeding kefir can effectively improve the estrogen deficiency caused by the phenomenon of bone loss. In order to reduce the side effects of long-term use of ALN and to evaluate the additive effect of combination therapy with kefir and ALN, we studied the effects of low-dose ALN (10 μg / kg) alone on the ovariectomized mice and ALN + kefir combination therapy in improving osteoporosis in ovariectomized mice. The results of this study showed that the combined use of ALN and Kefir can significantly increase bone mineral density (BMD), the trabecular bone volume and number of bone in the femoral cortical bone, significantly reduce the trabecular bone dispersion distance, and effectively delay bone loss.
目錄
摘要………………………………………………………i
Abstract…………………………………………………ii
圖次………………………………………………………vi
表次………………………………………………………viii
一、 緒論………………………………………………..1
二、 文獻探討…………………………………………..3
2.1 骨骼組織組成…………………………………………………………3
2.2 骨質疏鬆症……………………………………………………………4
2.3 骨質疏鬆症的臨床用藥………………………………………………6
2.4 骨質疏鬆症的動物模式………………………………………………8
2.5 研究動機與策略………………………………………………………11
三、 研究材料及方法……………………………..16
3.1 發酵乳及雙磷酸鹽藥物錠劑備製........................................................16
3.2實驗動物飼養…………………………………………………………17
3.3動物實驗設計與分組…………………………………………………18
3.4血液生化數值之測定…………………………………………………19
3.5電腦斷層股骨試片處理………………………………………………20
3.6 統計分析...............................................................................................21
四、 研究結果……….………………………………….22
4.1雌鼠體重變化........................................................................................22
4.2雌鼠子宮輸卵管外觀變化....................................................................22
4.3血液生化數值比較……………………………………………………23
4.4以電腦斷層掃描分析骨礦物密度……………………………………24
4.5骨體積與骨組織體積比 (BV/TV) 分析……………………………25
4.6骨表面積與骨體積比 (BS/BV) 分析………………………………26
4.7骨小樑微結構分析……………………………………………………27
4.8影像分析……………………………………………………………28
五、 討論及結論………………………………………30
參考文獻…………………………………………………33








圖次
圖1 骨骼重塑機制(bone remodeling) 示意圖……………………………43
圖2 去卵巢骨鬆大鼠經12週不同劑量之克弗爾(Kefir)及雙磷酸鹽
(ALN)治療後遠端股骨Micro-CT之橫向影像圖…..………......44
圖3 去卵巢骨鬆大鼠經12週不同劑量之克弗爾(Kefir)及雙磷酸鹽
(ALN)治療後遠端股骨Micro-CT之縱向影像圖……………..45
圖4 動物實驗流程………………………………………………………..46
圖5 實驗後小鼠的股骨影像圖…………………………………………..47
圖6 實驗期間老鼠體重之變化…………………………………………..48
圖7 實驗後各組老鼠的輸卵管和子宮外形……………………………..49
圖8 實驗後各組老鼠血清中的骨代謝指標……………………………..50
圖9 實驗後各組老鼠的股骨骨質密度(BMD)分析……………………..51
圖10 實驗後各組老鼠的股骨骨體積與骨組織體積比(BV/TV)分析….52
圖11 實驗後各組老鼠的股骨皮質骨表面積與骨體積比………………53
圖12 實驗後各組老鼠的股骨骨小樑平均厚度…………………………54
圖13 實驗後各組老鼠的股骨皮質骨影像圖……………………………55

圖14 實驗後各組老鼠的股骨骨小樑橫切面影像圖……………………56
圖15 實驗後各組老鼠的股骨骨小樑縱切面影像圖…………………57


















表次
表1 各式發酵乳產品之特殊菌元組成…………………………………...58
表2 實驗動物分組及給予之劑量………………………………………..59
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