臺灣博碩士論文加值系統

肥胖為全球關心的議題，在現代社會中，營養過剩普遍出現在高熱量密度食物與低能量消耗的生活型態中。肥胖是糖尿病、血脂異常、心血管疾病、癌症等疾病的危險因子，如何改善和預防肥胖的發生，成為一個重要的議題。安曼司石花菜 (Gelidium amansii) 為臺灣東北角一帶常見的紅藻，許多研究顯示石花菜萃取物可能具有抑制脂質堆積，降低血漿、肝臟脂質濃度及改善肥胖的能力。
為進一步了解其確切機制，本研究以雄性 Sprague Dawley (SD) 大白鼠進行為期八周的實驗，動物共四組，分別為 (1) 正常控制組 (Normal control diet, NC)、(2) 高脂飲食組 (High fat diet, HF)、(3) 石花菜熱水萃物組 (High fat diet + 5% Gelidium amansii hot-water extract, GHE)、(4) Cholestyramine 組 (High fat diet + 1% Cholestyramine, CH)，飼養期間皆採自由攝食。結果顯示，安曼司石花菜熱水萃物可以增加糞便脂質排出，降低血漿中總膽固醇及三酸甘油酯濃度，並改善肝臟及脂肪組織脂質堆積。安曼司石花菜熱水萃物能夠增加膽汁酸從糞便排出，活化肝臟 low density lipoprotein receptor (LDLR) 及 cholesterol 7 alpha-hydroxylase (CYP7A1) 蛋白表現，回收血漿 LDL-C 至肝臟並代謝成膽汁酸，改善血脂濃度。此外，安曼司石花菜熱水萃物藉由活化 AMP-activated protein kinase (AMPK) 及 farnesoid X receptor (FXR) 蛋白表現，抑制下游 acetyl-CoA carboxylase (ACC)、fatty acid synthase (FAS)、3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) 酵素活性及 peroxisome proliferator-activated receptor γ (PPARγ) 蛋白表現來減少肝臟脂質生合成及利用。GHE 促進 peroxisome proliferator-activated receptor α (PPARα) 蛋白表現量，增加肝臟內脂肪酸 β-oxidation。透過提升 microsomal triglyceride transfer protein (MTTP) 的活性，增加三酸甘油酯從肝臟排出，進而減少肝臟脂質堆積。在脂肪組織方面，GHE 可以促進脂解酵素 hormone sensitive lipase (HSL) 活性，減少三酸甘油酯堆積。綜合以上結果顯示，石花菜熱水萃物具有改善高脂飲食大白鼠脂質代謝能力。

Obesity is a global health concern. Nutrient excess marked by ubiquitous food of high palatability and caloric density and life styles requiring low energy output. It is a major risk factor for a number of metabolic diseases such as diabetes, dyslipidemias, cardiovascular disease, and certain cancers. How to improve and prevent the occurrence of obesity has become an important issue. Gelidium amansii is commonly used edible seaweed in Asian countries such as Taiwan, Korea, China and Japan. Recent studies have indicated that Gelidium amansii extract (GHE) may also have potential therapeutic implications for obesity. The extract of Gelidium amansii can inhibit lipid accumulation and reduce plasma and liver lipids. In order to investigate the effects of Gelidium amansii extract on lipid metabolism in rats. Male Sprague-Dawley (SD) rats were divided into 4 groups: (1) normal control diet (NC), (2) high fat diet (HF), (3) high fat diet + 5% Gelidium amansii hot water extract (GHE), and (4) high fat diet + 1% cholestyramine (CH). All the rats were fed the experimental diets and drinking water ad libitum for 8 weeks. The results showed that GHE significantly increased the excretion of lipid in the feces and decreased the levels of serum total cholesterol and triglyceride. It also improved lipid accumulation in liver and adipose tissue. We found that GHE could increase bile acid secretion in feces and activate hepatic low density lipoprotein receptor (LDLR) and cytochrome P450 7A1 (CYP7A1) protein expression. Its mechanisms might be to improve dyslipidemia by increasing clearance of plasma cholesterol and promoting bile acids synthesis from cholesterol in the liver. Moreover, GHE ameliorated hepatic protein levels associated with lipogenesis as well as activation of AMP-activated protein kinase (AMPK) and farnesoid X receptor (FXR), which inhibited the activities of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), HMG-CoA reductase (HMGCR) and eroxisome proliferator-activated receptor γ (PPARγ). Meanwhile, GHE increased β-oxidation of fatty acids by increasing the expressions of peroxisome proliferator activated receptor α (PPARα) in the liver. We also found that GHE could increase hepatic triglyceride excretion and reduced lipid accumulation through increasing microsomal triglyceride transfer protein (MTTP) activation. In adipose tissue, GHE was shown to increase hormone sensitive lipase (HSL) expression, which indicated that GHE reduced lipid accumulation by stimulating lipolysis via HSL elevation. Collectively, the results revealed that GHE may have great potential to improve lipid metabolism in high-fat-diet rats.

壹、 前言 1
貳、 文獻整理 2
一、 肥胖 (Obesity) 2
二、 高脂飲食 (High fat diet) 3
1. 定義 3
2. 實驗動物模式 3
3. 飲食中添加膽固醇與脂質代謝之相關性 4
三、 脂質代謝相關因子 4
1. 相關酵素 4
2. 基因蛋白 5
四、 腸壁黏膜影響 9
1. Mucinase 9
2. β-醛醣酸酶 (β-glucuronidase) 10
五、 石花菜 10
1. 海藻簡介 10
2. 海藻抗肥胖能力 10
3. 安曼司石花菜 (Gelidium amansii) 11
4. 石花菜熱水萃取物的結構與特性 11
5. 石花菜熱水萃取物對脂質代謝之影響 11
六、 藥物介紹 12
1. Cholestyramine 12
2. Cholestyramine 對脂質代謝之影響 12
參、 實驗設計 13
一、 實驗動機與目的 13
二、 實驗流程 13
三、 分析項目 14
四、 實驗材料 15
1. 實驗動物 15
2. 實驗飼料 15
3. 實驗樣品 15
4. 實驗儀器 15
五、 實驗方法 16
1. 實驗動物分組 16
2. 動物飼養與樣品收集 17
3. 飼料配方 17
4. 樣品分析 18
5. 統計分析 30
肆、 結果 31
一、 石花菜熱水萃物成份分析 31
二、 實驗期間大白鼠體重、攝食量和食物利用率之影響 31
三、 實驗結束犧牲時大白鼠組織臟器重量 31
四、 犧牲後大白鼠血漿生化指標測定結果 31
1. 血漿脂質濃度變化 31
2. 血漿 AST、ALT 活性、Adiponectin 及 GLP-1 濃度變化 31
五、 犧牲後大白鼠脂肪組織脂質濃度、脂解速率與 LPL 活性變化 32
六、 犧牲後大白鼠肝臟脂質濃度及脂質合成相關酵素活性測定結果 32
1. 肝臟脂質含量測定 32
2. 肝臟組織切片染色中脂肪空泡差異 32
3. 肝臟脂質合成相關酵素活性變化 32
七、 大白鼠肝臟蛋白質表現量測定結果 32
1. 肝臟 pAMPK/AMPK 及 FXR 之蛋白表現量 32
2. 肝臟 PPARα 及 PPARγ 之蛋白表現量 33
3. 肝臟 LDLR 及 MTTP 之蛋白表現量 33
4. 肝臟 CYP7A1 之蛋白表現量 33
八、 大白鼠糞便重量、糞便脂質排出量及細菌酵素測定結果 33
1. 糞便重量及脂質排出量濃度測定 33
2. 糞便細菌酵素活性測定 33
伍、 討論 34
一、 安曼司石花菜熱水萃物對大鼠體重、攝食量及組織臟器之影響 34
二、 安曼司石花菜熱水萃物對大白鼠血液生化數值之影響 34
三、 安曼司石花菜熱水萃物對大白鼠脂質代謝之影響 35
1. 對血漿脂質濃度之影響 35
2. 對肝臟組織脂質濃度之影響 35
3. 對脂肪組織脂質濃度之影響 36
4. 糞便脂質濃度之影響 37
四、 安曼司石花菜熱水萃物對大白鼠腸道細菌酵素之影響 37
陸、 結論 38
柒、 參考文獻 39

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