臺灣博碩士論文加值系統

代謝症候群是一種許多危險因子叢聚在一起的症狀，包含胰島素阻抗、內臟脂肪堆積、高血壓以及與糖尿病及心血管疾病有關之危險因子，如脂質及脂蛋白代謝異常，內皮細胞功能異常與發炎之因子產生等。代謝症候群在未來二十年內將成為心血管疾病及糖尿病流行率的指標。目前沒有一種單一食材能全面性的預防及改善與代謝症候群有關的多重危險因子，在本實驗中，將評估不同複方食材改善高果糖誘發代謝症候群大鼠之功效。
實驗將雄性SD大鼠分成四個組別，分別是空白組 (B)：餵食Chow diet；控制組 (C)：餵食高果糖飼料；食材處理組1 (T1)：除了餵食高果糖飼料外，並添加紅麴、大豆、苦瓜、甘草及綠藻；食材處理組2 (T2)：除了餵食高果糖飼料外，並添加紅麴、鰹魚萃取物、兒茶素及豆豉萃取物。本實驗持續進行16週。實驗期間分析血壓、禁食血漿血糖、胰島素、三酸甘油酯及膽固醇，並進行口服葡萄糖耐受性測試，觀察大鼠胰島素敏感性之變化。同時亦分析胰島素訊息傳遞相關蛋白在脂肪組織上的表現。
實驗結果顯示，C組之大鼠餵食高果糖造成禁食血漿葡萄糖、胰島素、三酸甘油酯、膽固醇濃度及收縮壓顯著增加。另外在口服葡萄糖耐受性測試中，發現C組大鼠之血漿葡萄糖與胰島素濃度之曲線下面積皆顯著大於B組。此現象與大鼠餵食高果糖後氧化壓力增加、胰島素受體受質-1及葡萄糖轉運蛋白4減少有關。
相較於C組，T1組之收縮壓、禁食血漿膽固醇和葡萄糖耐受性皆有改善的現象。另外在胰島素訊息傳遞蛋白方面，T1組之胰島素受體受質-1表現有增加的趨勢。而餵食T2組食材之大鼠，其收縮壓、禁食血漿三酸甘油酯、膽固醇濃度及胰島素敏感性皆有明顯改善。探討其機制，T2組之胰島素敏感性增加，原因可能與氧化壓力減少以及葡萄糖轉運蛋白4表現增加有關。

Metabolic syndrome (MS) is characterized by insulin resistance, visceral obesity, and hypertension as well as by a cluster of diabetic atherosclerosis risk factors including disturbed lipid and lipoprotein metabolism, endothelial dysfunction, and elevated pro-inflammatory cytokines. MS is likely to have a marked impact on the prevalence of cardiovascular disease and type 2 diabetes worldwide in the next two decades. It is evident that MS involves multiple risk factors and any single health food may not be effective in the prevention and improvement of MS. The objective of this study was to evaluate the effects of the supplementation of the various combinatorial foods on metabolic syndrome in a fructose-fed rat model.
The male SD rats were divided into four group: blank group (B), fed with standard Purina chow; control group (C), fed with high fructose diet alone; treatment 1 group (T1), fed with high fructose diet plus red yeast rice, soybean, bitter melon, licorice and green algae; treatment 2 group (T2), fed with high fructose diet plus red yeast rice, katsuobushi oligopeptide, catechin, and touchi extract. The study lasted for 16 weeks. Biochemical parameters related to blood pressure, fasting plasma glucose, insulin, triglyceride and cholesterol were measured, and an oral glucose tolerance test (OGTT) was performed in this study. The contents of insulin signaling pathway related proteins in adipose tissue were also determined.
Our data showed that, high fructose feeding cause significant increased in fasting plasma glucose, insulin, triglyceride, cholesterol and systolic blood pressure in group C. And the total area under curves for glucose and insulin in OGTT significantly increased in group C as compared with group B. To further investigated the possible mechanism of the metabolic defects induced by high fructose diet, we found that the rats showed increased oxidative stress and decreased expressions of insulin signaling pathway related protein, including insulin receptor substrate-1 and glucose transporter IV.
Compared with group C, systolic blood pressure, fasting plasma cholesterol and glucose tolerance were improved in group T1. And the total content of insulin receptor substrate-1 was raised in T1 group. The systolic blood pressure, fasting plasma triglyceride, cholesterol and glucose tolerance of rats in group T2 were ameliorated as well. The increased insulin sensitivity might result from the decreased oxidative stress and elevated expression of glucose transporter IV.

目錄
摘要 I
ABSTRACT II
誌謝 III
目錄 IV
表次 VII
圖次 VIII
壹、前言 1
貳、文獻回顧 2
第一節 代謝症候群 2
一、代謝症候群之簡介 2
二、代謝症候群之沿革 2
三、代謝症候群之診斷指標 3
四、代謝症候群之盛行率 5
五、代謝症候群之病理機制 6
六、代謝症候群之治療 8
第二節、胰島素訊息傳遞 9
一、胰島素 9
二、胰島素訊息傳遞路徑 11
三、胰島素阻抗 11
第三節、果糖誘發代謝症候群模式 12
第四節、過氧化體增生活化受體 (Peroxisome proliferator activated
receptor, PPAR) 之簡介 14
一、PPARα 14
二、PPARβ/δ 15
三、PPARγ 15
四、PPARs之ligands 16
第五節、選用食材介紹 18
一、紅麴 18
二、綠藻 18
三、苦瓜 19
四、大豆 20
五、甘草 20
六、兒茶素 21
七、鰹魚 21
八、豆豉 22
參、研究目的與實驗架構 23
第一節、研究目的 23
第二節、實驗架構 24
肆、材料與方法 25
第一節、實驗材料 25
一、實驗食材 25
二、化學藥品與試劑 25
(一) 化學藥品 25
(二) 溶劑 26
(三) 酵素套組 27
(四) 飼料組成 27
(五) 抗體 28
第二節、儀器設備 28
第三節、實驗方法 30
一、實驗動物 30
二、實驗分組及飼養 30
三、食材劑量選擇方法 31
(一) 食材處理組1 31
(二) 食材處理組2 31
四、血壓之測量 37
五、禁食狀態血液之採集與處理 37
(一) 血漿葡萄糖濃度之測定 37
(二) 血漿胰島素濃度之測定 37
(三) 三酸甘油酯濃度之測定 38
(四) 膽固醇濃度之測定 38
六、口服葡萄糖耐受性試驗 (Oral glucose tolerance test, OGTT) 39
七、動物犧牲與檢體之收集與分析 39
(一) 動物檢體收集與處理 39
(二) 動物犧牲後之生化分析項目 40
(三) 血糖調控相關蛋白質含量之測定 44
第四節、統計分析 47
伍、結果 48
一、生長狀況 48
二、飼養期間禁食血漿葡萄糖濃度之變化 48
三、飼養期間禁食血漿胰島素濃度之變化 48
四、飼養期間禁食血漿三酸甘油酯濃度之變化 48
五、飼養期間禁食血漿膽固醇濃度之變化 49
六、飼養期間血壓之變化 49
七、口服葡萄糖耐受性測試 49
八、組織臟器重量 51
九、犧牲禁食血漿分析 52
十、肝臟三酸甘油酯、膽固醇及TBARS分析 52
十一、脂肪組織胰島素訊息傳遞相關蛋白質表現量 53
陸、討論 54
柒、結論 60
捌、參考文獻 76

表次
表4-1、各組飼料組成成份 32
表4-2、Rodent Chow diet的組成 33
表4-3、55%高果糖飼料之組成 34
表4-4、食材處理組1飼料之組成 35
表4-5、食材處理組2飼料之組成 36
表5-1、大鼠於第4、8和15週時進行口服葡萄糖耐受性試驗血漿葡萄糖和
胰島素濃度曲線下面積及HOMA-IR值 72
表5-2、大鼠飲食處理16週後之組織臟器重量 73
表5-3、大鼠飲食處理16週後之禁食血漿葡萄糖、胰島素、三酸甘油酯、膽固醇、高密度脂蛋白與TBARS濃度 74
表5-4、大鼠飲食處理16週後之肝臟三酸甘油酯、膽固醇與TBARS含量 75

圖次
圖2-1、果糖在肝臟之代謝 13
圖2-2、PPAR之結構與轉錄活化 17
圖3-1、本論文之實驗架構 24
圖5-1、大鼠飲食處理16週期間體重變化之情形。 61
圖5-2、大鼠飲食處理16週期間禁食血漿葡萄糖變化之情形。 62
圖5-3、大鼠飲食處理16週期間禁食血漿胰島素變化之情形。 63
圖5-4、大鼠飲食處理16週期間禁食血漿三酸甘油酯變化之情形。 64
圖5-5、大鼠飲食處理16週期間禁食血漿膽固醇變化之情形。 65
圖5-6、大鼠飲食處理16週期間血壓變化之情形 66
圖5-7、實驗4週後大鼠進行口服葡萄糖耐受性試驗血漿葡萄糖 (A) 及胰島素濃度 (B) 之變化。 67
圖5-8、實驗8週後大鼠進行口服葡萄糖耐受性試驗血漿葡萄糖 (A) 及胰島素濃度 (B) 之變化。 68
圖5-9、實驗15週後大鼠進行口服葡萄糖耐受性試驗血漿葡萄糖 (A) 及胰島素濃度 (B) 之變化。 69
圖5-10、大鼠飲食處理16週後大鼠脂肪組織中胰島素訊息傳遞相關蛋白質表現量。 70
圖5-11、大鼠飲食處理16週後脂肪細胞中訊息傳遞相關蛋白質表現量之定量結果。 71

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