臺灣博碩士論文加值系統

本研究主要探討高分子量幾丁聚醣與魚油對於高脂飲食脂肪肝影響之機制探討。以Sprague-Dawley (SD) 大白鼠為實驗動物，實驗共分為五組，分別為 (1)正常飲食組 (Normal control diet, ND) (2) 高脂飲食組 (High fat diet, HF) (18%lard+2%soybean) (3) 高脂飲食中添加 5% 魚油組 (HF + 5% fish oil, HO) (13%lard+2%soybean+5% fish oil) (4) 高脂飲食中添加 5% 幾丁聚醣組 (HF + 5% chitosan) (18%lard+2%soybean+5% chitosan, 5CH) (5) 高脂飲食中添加 5% 幾丁聚醣組及 5% 魚油組 (5% chitosan + HO, 5CHO)，實驗共進行五週，飼養期間大白鼠採自由攝食。實驗結果顯示，攝取幾丁聚醣與魚油明顯抑制肥胖大白鼠體重、肝臟重量以及脂肪組織重量，其中以攝取 5% 幾丁聚醣與魚油效果最為顯著。在血漿生化值方面，攝取 5% 幾丁聚醣與魚油能降低 AST、ALT 活性和總膽固醇含量，並降低 TC/HDL-C 的比值。在肝臟脂質方面，攝取 5% 幾丁聚醣與魚油能提升肝臟 AMPKα 活性，而能抑制下游肝臟和腎周脂肪組織Lipogenic transcription factors 蛋白表現，並抑制 SREBP2 和 HMGR 基因表現，降低肝臟膽固醇生成，另一方面，能提升 PPARα 蛋白表現，使其下游 Fatty acid oxidation 和 HDL-biogenesis 的基因表增加，而增加 Cholesterol efflux，以上結果顯示幾丁聚醣與魚油能調控肝臟脂質代謝。此外幾丁聚醣與魚油會抑制血漿 ANGPTL4 及 APOC3 蛋白表現，並促進肝臟 MTTP 及 APOE 表現來增加 VLDL 的分泌，達到改善脂肪肝之功效。在脂肪組織變化方面，攝取幾丁聚醣與魚油能有效抑制抑制腎周脂肪組織三酸甘油酯堆積，降低腎周脂肪組織 LPL 活性並促進脂解作用，進而減少腎周脂肪組織 TG 含量，同時能抑制腎周脂肪組織細胞增大。綜合以上論述，幾丁聚醣與魚油能提升 LXRα 和 PPARα 蛋白表現，進而達到改善高脂飲食產生之脂肪肝和肥胖的作用。

The purpose of this study is to investigate the mechanism of chitosan with fish oil on improving fatty liver in rats induced by high fat diet (18% lard + 2% soybean oil + 0.5% cholesteerol). Male Sprague-Dawely rats divided into five group : (1) normal control diet (ND), (2) high fat diet (HF) (18% lard + 2% soybean oil), (3) high fat diet with 5% fish oil (HO) (13% lard + 2% soybean oil + 5% fish oil), (4) high fat diet + 5% chitosan (5CH), (5) 5% chitosan + HO (5CHO) (13% lard + 2% soybean oil + 5% fish oil). All the rats were fed the experimental diets and drinking water ad libitum for 5 weeks. Chitosan and fish oil significantly decreased body, liver weight and adipose tissue weight in obesity rats. It was interesting to note that 5CHO group significantly decreased plasma ANGPTL4 and APOC3 protein expression, increased hepatic MTTP and APOE protein expression, indicating that it will promote VLDL secretion. In plasma, 5CHO group significantly decreased plasma TG and TC levels and decreased TC/HDL-C ratio. In addition, 5CHO group significantly elevated activity of AMPKα and inhibited downsteam protein of lipogenic transcription factors LXRα mRNA expression and decreased liver cholesterol biosynthesis. On the other hand, 5CHO group significantly elevated PPARα protein expression and increased fatty acid oxidation and reverse cholesterol transport gene expression. Chitosan and fish oil supplementation decrease the accumulation of TG in perirenal adipocyte. Results from this study suggest thatchitosan and fish oil combination ameliorate fatty liver via affecting genes and protein expression to regulate lipid metabolism in liver.

壹、 前言 1
貳、 文獻整理 3
一、肥胖症 (obesity) 3
1. 肥胖症的現況與定義 3
2. 肥胖與脂肪組織之關聯性 4
二、脂肪肝 (Fatty liver) 7
1. 脂肪肝之定義 7
2. 非酒精性脂肪肝病的致病機轉 7
3. 肝臟VLDL之分泌作用 (VLDL secretion) 9
三、高脂飲食 12
1. 定義 12
2. 高膽固醇飲食對脂質代謝之影響 13
3. 脂質代謝相關酵素 14
4.脂質代謝相關基因蛋白 16
四、幾丁質與幾丁聚醣 21
1. 幾丁質之來源與分佈 21
2.幾丁質與幾丁聚醣之結構 22
3. 幾丁質與幾丁聚醣之特性 23
4.幾丁聚醣之應用 23
5.幾丁聚醣對於脂質代謝之影響 24
五、膳食魚油 25
1.魚油對於脂質代謝之影響 25
2.魚油對於體內抗氧化之作用 27
六、AMP-activated protein kinase (AMPK) 之簡介 28
七、LXR (Liver X Receptor) 29
八、APOC3 (Apo-lipoprotein C3) 30
九、Uncoupling proteins (UCPs) 家族之介紹 31
參、 實驗設計 34
1.實驗動機 34
2.實驗流程 34
肆、 實驗材料 36
1. 實驗動物 36
2. 實驗飼料 36
3. 幾丁聚醣 36
4. 實驗儀器 36
伍、 實驗方法 38
1. 幾丁聚醣去乙醯度、黏度及平均分子量之測定 38
2. 動物分組 39
3. 動物飼養及樣品收集 39
4. 飼料配方 40
5. 樣品分析 40
陸、 結果 56
柒、 討論 60
捌、 結論 64
玖、 參考文獻 65

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