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研究生:邱永偉
研究生(外文):Yung-Wei Chiu
論文名稱:七層塔水萃物保護雌性大鼠在雌激素缺乏誘發肥胖之功效
論文名稱(外文):Protective Effects of Aqueous Ocimum gratissimum Extract on the Estrogen Deficiency-induced Obesity
指導教授:賴德仁賴德仁引用關係
指導教授(外文):Te-Jen Lai
學位類別:博士
校院名稱:中山醫學大學
系所名稱:醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:英文
論文頁數:93
中文關鍵詞:停經期代謝徵候群脂肪代謝肥胖七層塔卵巢去勢毒性測試
外文關鍵詞:menopausemetabolic syndromelipid metabolismobesityOcimum gratissimumovariectomytocixity test
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婦女停經過渡期,首先是雌激素血中濃度下降,其次是身體成分和分佈產生顯著變化,從周邊重新分配到中央的囤積。中央型肥胖與胰島素抗性及血脂肪失調有關連性,並會增加心血管疾病的危險。然而,婦女停經後肥胖的機理仍然不清楚。七層塔(Ocimum gratissimum L.),自古以來在許多國家為食用香料或為傳統草藥,具有明顯的芳香的風味和豐富的抗氧化成分擁有多種治療功能。在本研究中,我們透過使用卵巢去勢(OVX)和高脂肪膽固醇飲食(HFCD)的動物實驗模型,評估七層塔萃取物(OGE)預防肥胖和高血脂的功效。七層塔萃取物也用毒性試驗來評估其安全性。結果顯示,在與假手術組大鼠體重增加相比,卵巢去勢大鼠的體重有增加的現象。OGE(0.2毫克/毫升)、雌二醇苯甲酸酯(EB,0.025毫克/公斤)和膠原(2.5毫克/毫升)顯著減少卵巢去勢大鼠增強的體重,而低劑量的OGE和膠原蛋白卻不能回復體重。高劑量OGE和膠原以及EB也能回復在卵巢去勢大鼠性腺周邊脂肪組織內的脂肪細胞尺寸的增大。此外,在高脂肪和高膽固醇動物實驗模型,兩種劑量的OGE(20毫克/公斤和10毫克/公斤)都可以減少HFCD大鼠血漿中的低密度脂蛋白膽固醇,總膽固醇和甘油三酯的含量。在毒性試驗中,觀察正常肝細胞存活率測試和在Physa acuta的胚胎發育都顯示OGE是無毒性的。這些結果推測,在控制體重和改善更年期婦女的脂質的代謝方面,七層塔水萃物是一有效用的膳食補充劑。

The menopausal transition in women, starting with declining estrogen levels, is followed by significant changes in body composition and distribution, which is redistributed from peripheral to a more central accumulation. Central obesity has been linked with insulin resistance, dyslipidemia, and increased risk for cardiovascular disease. However, the mechanism of post-menopausal obesity remains far from clear. Ocimum gratissimum L., as food spice or traditional herb in many countries, has strong-smelling aromatic flavor and is rich in antioxidants which possess anti-inflammation activity and a multitude of other therapeutic functions. In this study, by using the ovariectomized (OVX) and high fat-cholesterol diet (HFCD) animal models, we evaluate the effects of Chinese herb Ocimum gratissimum extract (OGE) in preventing obesity and hyperlipidemia. Safety of OGE is also evaluated by toxicity tests. The results showed that the increase of body weight in OVX rats was enhanced as compared to that in the sham-operated rats. OGE (0.2 mg/ml), estrodial benzoate (EB, 0.025mg/kg), and collagen (2.5 mg/ml) all significantly reduced the enhanced body weight gain in OVX rats, while the lower dose of OGE and collagen cannot reverse the weight gain. Moreover, the higher dose of OGE and collagen as well as EB also reversed the increased size of adipocyte of perigonadal adipose tissue in OVX rats. In the high-fat and high-cholesterol model, both doses of OGE (20 mg/kg and 10 mg/kg) can significantly reduce the increase in plasma levels of LDL-cholesterol, total-cholesterol and triglyeride in the HFCD rats. In the tocixity tests, no cytotoxicity activity of OGE was observed in the normal liver cell viability test and in embryo development of the freshwater snail “Physa acuta”. These results suggest that a dietary supplement of OGE may be useful for controlling the body weight and improving lipid metabolism of postmenopausal women.

TABLE OF CONTENT
LIST OF ABBREVIATONS 1
中文摘要 2
ABSTRACT 3
1. INTRODUCTION 1
1.1. Metabolic syndrome in post-menopausal women 1
1.2. Inflammation in menopausal women 5
1.3. Herbal medicines used in the treatment of obesity 6
1.4. Ocimum gratissimum L 9
1.5. Obesity in ovariectomized rat model and Motivation 12
2. MATERIALS AND METHODS 14
2.1 Preparation of OGE and Composition Analysis 14
2.2 Model of ovariectomizied Sprague Dawley rat 15
2.2.1. Experiment design 15
2.2.2. Histological analysis of adipose tissue and cell size determination 17
2.2.3. Measurement of serum biochemical makers 17
2.2.4. Measurement of bone mineral density (BMD) 17
2.2.5. Oral glucose tolerance test (OGTT) 18
2.2.6. Statistical analysis 18
2.3 Model of high fat/cholesterol diet-fed hamster 18
2.3.1. Animals and care. 18
2.3.2. Preparation of diet and supplement 18
2.3.3. Experimental design and data collection 19
2.3.4. Serum lipid profile estimation 20
2.3.5. Statistical analysis 20
2.4 Cell experiments 20
2.4.1. Cell Culture and Experimental Treatments 20
2.4.2. Cell Viability Assay 21
2.5. Toxicity testing by Physa acuta 21
3. RESULTS 22
3.1 OGE against the estrogen deficiency-induced obesity 22
3.2 Estrogen and OGE against the estrogen deficiency-induced obesity 23
3.3 Collagen against the estrogen deficiency-induced obesity 24
3.4 Collagen and OGE against the estrogen deficiency-induced obesity 25
3.5 Oral-treated OGE against the estrogen deficiency-induced obesity 26
3.6 The effect of oral-treated OGE on the high-fat-diet-induced hypercholesterolemia 26
3.6.1. Body weight gain, food consumption and clinic observation of hamsters 27
3.6.2. Induction of hyperlipidaemia with high cholesterol diet 27
3.6.3. Effects of aqueous Ocimum grastisimmun extract and statin on plasma lipid profile 28
3.7 The toxicity test of OGE in the liver normal and cancer cells 28
3.8 The toxicity test of OGE in the Physa acuta embryos. 29
4. DISCUSSION 30
4.1. OGE reduced the estrogen deficiency-induced obesity 30
4.2 Lipid-lowing and hypocholesterolemic effects of OGE on high fat/cholesterol diet-fed hamster 31
4.3 The toxicity test of OGE in the liver normal and cancer cell lines 33
5. REFERENCE 34
6. FIGURES AND TABLE 58



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