臺灣博碩士論文加值系統

本研究係探討魚油中添加全反式視網酸 (all-trans retinoic acid；ATRA)對小鼠體內脂質代謝產生的影響。以40隻C57BL/6J小鼠為研究對象並隨機分為四組：魚油組 (FO)、大豆油組 (SO)、魚油添加ATRA組 (FR)、大豆油添加ATRA組 (SR)，四組油脂均給予27% (w/w)，FR和SR額外添加66.7 mg/kg diet 的ATRA。實驗期四個月後，分析肝臟和血液中三酸甘油酯 (TG)、總膽固醇 (TC)、低密度脂蛋白膽固醇 (LDL-C)、高密度脂蛋白膽固醇 (HDL-C)、游離脂肪酸濃度 (NEFA)，Fatty acid synthase (FAS)、Acyl-CoA oxidase (ACO)、Acetyl-CoA carboxylase (ACC)、catalase等酵素活性，與肝臟PPAR (peroxisome proliferator activated receptor)δ、RAR (retinoic acid receptor)α蛋白表現量，並將肝臟和白色脂肪組織取出做H＆E染色。結果顯示魚油能顯著降低體重、肝脂質及FAS活性，並增加PPARδ蛋白質表現。而全反式視網酸的添加對於降低體重、血脂及肝脂質具有加成之效果。由上述結果推論，魚油能較大豆油增加PPARδ蛋白表現，而全反式視網酸的給予能更有效降低血液和肝臟脂質並增加RARα表現，加速脂質分解、減少脂質合成反應之進行。

The aim of this study was to assess the fish oil plus all-trans retinoic acid (ATRA) on lipid metabolism in mice. Forty C57BL/6J male mice were divides into fish oil (FO), soybean oil (SO) , fish oil plus ATRA (FR), soybean oil plus ATRA (SR) four groups. After four months, liver and serum triglyceride, total cholesterol, LDL-C, HDL-C, free fatty acids were analyzed, liver PPAR (peroxisome proliferator-activated receptor) delta, RAR (retinoic acid receptor) alpha protein expression and FAS (fatty acid synthase), ACO (acyl-CoA oxidase), ACC (acetyl-CoA carboxylase), catalase enzymes activity were also measured. The results demonstrated fish oil had lower concentration in the liver and serum triglyceride, total cholesterol, and FAS activity also significantly decreased. The liver PPAR delta expression was higher in FO group. And oil plus all-trans retinoic acid had more efficiency in lower body weight, liver and blood lipids. Supplement with all-trans retinoic acid also increased retinoic acid receptor α protein expression. In conclusion that fish oil can increase the PPAR delta expression, moreover fish oil plus ATRA can be more effectively to reduce blood and liver lipids. This will help to reduce weight gain and prevent obesity.

中文摘要..............................................................Ι
英文摘要 (Abstract)...................................................Π
致謝................................................................Ⅲ
目錄................................................................Ⅴ
表目錄................................................................VIII
圖目錄.............................................................IX
第一章 緒論.........................................................1
第二章 文獻回顧......................................................3
第一節、魚油..........................................................3
一、魚油和n-3多元不飽和脂肪酸.....................................3
二、魚油影響脂質代謝可能機制......................................3
三、不同魚油劑量對於脂質代謝的影響.................................5
第二節、PPARs (peroxisomal proliferator-activated receptors)......5
一、PPARs介紹...................................................5
二、PPARs的作用機制.............................................6
三、PPARs isoform..............................................7
第三節、魚油和PPARs...............................................9
第四節、All-trans retinoic acid..................................11
一、All-trans retinoic acid 介紹..............................11
二、Retinoic acid和retinoid receptors........................11
第五節、RAR、PPARs及adipogenesis................................12
第三章 實驗設計與材料方法............................................13
第一節、實驗流程..................................................13
第二節、實驗材料..................................................14
一、實驗動物和飼養方法..........................................14
二、飼料組成與配製..............................................14
三、劑量設計概念................................................17
第三節、分析項目及方法............................................18
一、動物犧牲及樣品收集..........................................18
二、血脂質分析.................................................19
三、肝臟脂質分析................................................23
四、酵素活性測定................................................26
五、油脂脂肪酸分析..............................................35
六、白色脂肪組織中全反式視網酸濃度分析............................36
七、以西方墨點法分析肝臟中PPARδ蛋白質含量.........................37
八、生殖腺週圍白色脂肪組織及肝臟組織H＆E (hematoxylin and eosin solution) .........................................................42
第四節、統計分析.................................................42
第四章、實驗結果.....................................................43
第一節、動物攝食和生長狀況.........................................43
第二節、血脂質濃度分析............................................47
第三節、肝臟脂質分析..............................................54
第四節、肝臟中酵素活性測定.........................................59
第五節、小鼠副睪白色脂肪組織外觀、肝臟、副睪白色脂肪組織 切片.........65
第六節、白色脂肪組織中全反式視網酸濃度..............................70
第七節、大豆油和魚油脂肪酸組成分析..................................70
第八節、魚油及大豆油對於小鼠肝臟中PPARδ蛋白質表現之影響...............73
第五章、討論.........................................................76
第一節、實驗飲食對於C57BL/6J小鼠體重和組織重量之影響.................76
第二節、實驗飲食對於C57BL/6J小鼠血脂質、肝脂質及酵素活性影響..............78
第三節、實驗飲食對於小鼠肝臟和白色脂肪組織切片影響........................81
第六章、結論.........................................................83
第七章、參考文獻......................................................84
附錄一..............................................................94表目錄
表3-1 實驗飼料組成..............................................................................16
表4-1 四種實驗飲食所提供每日蛋白質、脂質、醣類、熱量及全反式 視網酸攝取量..............................................................................44
表4-2 第0、30、60、90、120天各組老鼠體重.........................................45
表4-3 各組老鼠組織重量......................................................................46
表4-4 魚油和大豆油脂肪酸組成...........................................72
圖目錄
圖4-1 小鼠血清中三酸甘油酯濃度..............................................49
圖4-2 小鼠血清中總膽固醇濃度..................................................50
圖4-3 小鼠血清中游離脂肪酸濃度..............................................51
圖4-4 小鼠血清中低密度脂蛋白膽固醇濃度..............................52
圖4-5 小鼠血清中高密度脂蛋白膽固醇濃度..............................53
圖4-6 小鼠每克肝臟中三酸甘油酯含量......................................56
圖4-7 小鼠每克肝臟中總膽固醇含量..........................................57
圖4-8 小鼠每克肝臟中游離脂肪酸含量......................................58
圖4-9 小鼠肝臟中fatty acid synthase活性測定.................................61
圖4-10 小鼠肝臟中acyl-CoA carboxylase活性測定...........................62
圖4-11 小鼠肝臟中Acyl-CoA oxidase活性測定.................................63
圖4-12 小鼠肝臟中catalase活性測定..................................................64
圖4-13 小鼠生殖腺週邊白色脂肪組織外觀觀察................................67
圖4-14以H＆E染色觀察小鼠生殖腺週邊白色脂肪組織、肝臟組織切片..........................................................................................................68
圖4-15 以oil red’O 染色觀察小鼠肝臟組織切片...............................69
圖4-16 小鼠白色脂肪組織中全反式視網酸濃度................................71
圖4-18以西方墨點法分析小鼠肝臟中PPARδ表現..........................74
圖4-19以西方墨點法分析小鼠肝臟中RARα表現.............................75

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