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研究生:孔琳婧
研究生(外文):Lin-Jing Kong
論文名稱:三價鉻離子與雌二醇對絕育後雌性大鼠骨代謝的影響
論文名稱(外文):Effects of trivalent chromium and estradiol on bone metabolism in ovariohysterectomized rats
指導教授:李衛民李衛民引用關係
指導教授(外文):Wei-Ming Lee
口試委員:吳瑞德赖政宏
口試日期:2018-01-11
學位類別:碩士
校院名稱:國立中興大學
系所名稱:獸醫學系暨研究所
學門:獸醫學門
學類:獸醫學類
論文種類:學術論文
論文出版年:2018
畢業學年度:106
語文別:英文
論文頁數:72
中文關鍵詞:三價鉻離子雌二醇骨代謝
外文關鍵詞:trivalent chromiumestradiolbone metabolism
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在絕經後婦女,由於雌激素水平的迅速降低,骨質疏鬆、糖尿病、肥胖等代謝性疾病的發病率明顯增加。絕經後骨質疏鬆症的發生,除了因為雌激素對於骨代謝的直接調節以外,可間接作用於骨代謝的糖尿病、肥胖等疾病的影響亦不可忽視。對於絕經後婦女骨質疏鬆症的治療,傳統上採用荷爾蒙替代療法,即給病患提供維持劑量的雌激素。另一方面,三價鉻離子因其具有調節糖代謝、蛋白質代謝和脂質代謝的功效而被廣泛應用於二型糖尿病的治療。然而,目前尚未有研究證實單獨補充三價鉻離子或是將其與荷爾蒙替代療法合併使用是否會對骨密度造成影響。因此,本研究的目的即在於探討單獨使用三價鉻離子及將其與雌二醇併用時對於絕育後雌性大鼠骨代謝的影響。實驗採用了36隻八周齡的雌性SD大鼠,在實施子宮卵巢摘除術後隨機分成六組:對照組(Control),進行子宮卵巢摘除術後以生理鹽水灌胃;鉻離子組(Cr),進行子宮卵巢摘除術後以三價鉻離子溶液灌胃;低劑量雌二醇組(LE2),進行子宮卵巢摘除術後以維持劑量的雌二醇溶液灌胃;低劑量雌二醇加鉻離子組(LE2+Cr),進行子宮卵巢摘除術後以維持劑量的雌二醇與三價鉻離子混合溶液灌胃;高劑量雌二醇組(HE2),進行子宮卵巢摘除術後以二十倍於維持劑量的雌二醇溶液灌胃;高劑量雌二醇加鉻離子組(HE2+Cr),進行子宮卵巢摘除術後以二十倍於維持劑量的雌二醇與三價鉻離子混合溶液灌胃。實驗期間每週稱取大鼠體重並記錄。於實施子宮卵巢摘除術十五周後犧牲大鼠,收集血液樣本測量鈣(Ca)、磷(P)、副甲狀腺素(PTH)及骨鈣蛋白(OC)的濃度以評估骨代謝;取雙側的股骨和脛骨測量松質骨含量(BV/TV)以評估骨密度。結果顯示,在未添加鉻離子的三個實驗組(Control,LE2和HE2組)中,相對體重增長率(VarBW)、骨松質含量(BV/TV)以及PTH含量這三個因素與雌激素劑量具有相關性;其中只有高劑量雌二醇組(HE2)具有明顯的預防骨質疏鬆的作用(以松質骨含量作為評估標準)。在所有的被測項目中,鉻離子組(Cr)與低劑量雌二醇組(LE2)具有相似的結果。但是,當將三價鉻離子與雌二醇併用時,鉻離子會將原本存在於不同劑量雌二醇組間的差異縮小。綜合以上結果,單獨使用三價鉻離子在調節骨代謝方面具有與單獨給予維持劑量的雌二醇類似的功效;將三價鉻離子與維持劑量的雌二醇合並使用亦不會造成明顯差異。但是,若將三價鉻離子與高劑量雌二醇併用,則會削弱高劑量雌二醇的骨保護作用。
In postmenopausal women, the dramatic decrease of estrogen results in a high morbidity of osteoporosis as well as other metabolic disorders like diabetes and obesity. Apart from the direct effect of estrogen on bone metabolism, diabetes and obesity also affect it indirectly. The traditional treatment of women postmenopausal osteoporosis is hormone replacement therapy (HRT), a supplement of maintaining dose estradiol (E2). Trivalent chromium (Cr3+), for its benefit to carbohydrate, protein and lipid metabolism, is widely used in the treatment of type 2 diabetes mellitus. However, whether a supplement of Cr3+ alone or combined with HRT will make some differences on bone mineral density remains uninvestigated. Therefore, the aim of this study is to figure out the effects of Cr3+ alone and combined with E2 on bone metabolism in the model of ovariohysterectomized rats. Thirty-six 8-week-old female Sprague-Dawley rats were randomly divided into 6 groups after ovariohysterectomy: Control (administration of saline), Cr (Cr3+ supplement only), LE2 (a supplement of maintaining-dose E2 only), LE2+Cr (a supplement of maintaining-dose E2 with Cr3+), HE2 (a supplement of 20X maintaining-dose E2 only) and HE2+Cr (a supplement of 20X maintaining-dose E2 with Cr3+). Body weight was measured weekly during 15 weeks’ experiment. Plasma Calcium (Ca), Phosphorus (P), parathyroid hormone (PTH) and osteocalcin (OC) concentrations were measured to evaluate bone metabolism. Bilateral femurs and tibiae were dissected to measure trabecular bone percent (BV/TV%). The results showed an E2-dose-related relationship in variant body weight ratio (VarBW), PTH and BV/TV within None Cr groups (Control, LE2 and HE2 groups) and only high-dose E2 had a significant (P<0.05) effect on preventing osteoporosis according to BV/TV. The Cr group shared similar data (P>0.05) with LE2 group on all the parameters. Moreover, an addition of Cr3+ tended to narrow the E2-dose-related difference between None Cr groups. It is indicated that Cr3+ has an effect on bone metabolism similar to maintaining-dose E2, as well as the combination of Cr3+ and maintaining-dose E2. However, an addition of Cr3+ can weaken the bone protection effect of high-dose E2.
摘要 i
Abstract ii
Content iii
List of table v
List of figure vi
Chapter 1 Introduction 1
Chapter 2 Literature review 2
2.1. Bone anatomy and metabolism 2
2.1.1. The general anatomy of long bone 2
2.1.2. The constituent of bone 4
2.1.3. Bone remodeling 9
2.1.4. Bone homeostasis 10
2.1.5. Calcium and Phosphorus Metabolism 15
2.2. Chromium 17
2.2.1. Physiology of chromium 17
2.2.2. The effect of Chromium on bone metabolism 18
Chapter 3 Materials and methods 22
3.1. Animals 22
3.2. Experimental design 22
3.3. Variant body weight ratio % (VarBW%) calculation 24
3.4. Histology and histomorphometric evaluations 24
3.5. Plasma measurement 25
3.5.1. Biochemical parameters 25
3.5.2. Hormone parameters 25
3.6. Statistical analysis 26
Chapter 4 Results 28
4.1. The final variant body weight ratio % (VarBW%) 28
4.2. Histology evaluations of trabecular bone structure 28
4.3. Histomorphometric evaluations (BV/TV%) of trabecular bone structure 29
4.3.1. Trabecular bone structure in proximal metaphysis of tibia 29
4.3.2. Trabecular bone structure in distal metaphysis of femur 30
4.3.3. Comparison of BV/TV (%) between tibial proximal metaphysis and femoral distal metaphysis 30
4.3.4. Correlation between BV/TV of tibial proximal metaphysis and femoral distal metaphysis against the final variant body weight ratio (VarBW) 31
4.4 The plasma concentration of bone remodeling markers 31
4.4.1. The plasma concentration of Calcium 31
4.4.2. The plasma concentration of Phosphorus 32
4.4.3. The product of plasma concentration of Calcium and Phosphorus 32
4.4.4. The plasma concentration of parathyroid hormone (PTH) 33
4.4.5. The plasma concentration of osteocalcin (OC) 34
4.4.6. Correlation among BV/TV of tibial proximal metaphysis and femoral distal metaphysis and variant body weight ratio (VarBW) 34
4.4.7. Correlation among BV/TV of tibial proximal metaphysis and femoral distal metaphysis and plasma measurements of bone remodeling 35
4.4.8. Correlation among plasma measurements of bone remodeling 35
Chapter 5 Discussion 55
5.1. The effect of estradiol in different dosages on bone metabolism (comparison among None E2 groups) 55
5.2. The effect of Trivalent Chromium combined with estradiol in different dosages on bone metabolism 57
5.3. Correlation between BV/TV and other parameters 59
5.4. Correlation among plasma measurements of bone remodeling 60
5.5 Conclusion 61
Reference 63
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