臺灣博碩士論文加值系統

代謝症候群是由數種代謝異常結合於同一人身上的疾病。研究指出，代謝症候群的患者，得到糖尿病、心臟病的機率與死亡率會大幅增加。故本實驗將利用複方食材，評估其改善代謝症候群之功效。
實驗設計將雄性SD大鼠分成四組，分別是空白組 (B)：餵飼50%玉米澱粉和10%蔗糖混和飼料；控制組 (C)：餵飼60%高果糖飼料；食材處理組1 (T1)：餵飼高果糖飼料，並添加紅麴、大豆、綠藻、苦瓜及甘草複方。食材處理組2 (T2)：同樣餵飼高果糖飼料，並添加兒茶素、豆豉、鰹魚及綠藻複方。實驗持續進行13週。實驗期間分析血壓、禁食血漿血糖、三酸甘油酯 (TG)、總膽固醇 (TC)、高密度脂蛋白膽固醇 (HDL-C)、低密度脂蛋白膽固醇 (LDL-C) 及與胰島素訊息傳遞相關蛋白之磷酸化活性表現量。實驗期間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。
實驗結果顯示，C組之血壓、TC、TG、LDL-C濃度、肝臟總膽醇濃度皆顯著較B組高。而胰島素敏感性與高密度脂蛋白膽固醇比例 (HDL-C/TC) 則顯著低於 B 組，代表C組產生了代謝症候群之現象。探討其機制，C組之insulin receptor (IR) 及Akt的磷酸化量和Glucose transportor 4 (Glut 4) 表現量與B組比較皆有下降的趨勢。相較於C組，T1組具有較高的HDL-C/TC和胰島素敏感性，較低的血壓、TG與腹部脂肪。而其IR、insulin receptor substrate-1 (IRS-1)、Akt及Glut 4之表現量和Akt活化量與C組比較皆有上升的趨勢。T2組則有較高的HDL-C/TC、胰島素敏感性，與較低的血壓、三酸甘油酯和總膽固醇濃。且其IR、Akt及Glut 4之表現量和Akt活化量與C組比較亦皆有上升的趨勢。顯示本實驗使用之複方食材可有效改善代謝症候群之症狀。
另本實驗中所使用的空白組飼料非一般常用的 chow diet，因此，我們另設計一實驗比較兩種飼料的大鼠的影響。實驗設計將雄性SD大鼠分成兩組，分別是實驗組 (Co)：餵飼餵飼50%玉米澱粉和10%蔗糖混和飼料；對照組 (Ch)：餵食chow diet。實驗結果顯示，Co組之腹部脂肪、TC、TG及胰島素濃度皆顯著較Ch組高。推測原因可能與微量礦物質、脂質、脂肪酸種類及蔗糖有關。

The metabolic syndrome is a common metabolic disorder on the person body. The previous study showed that the presence of the syndrome predicted increased cardiovascular disease and coronary heart disease mortality. The objective of this study was to evaluate the effects of the supplementation of the combinatorial health food on metabolic syndrome in a fructose-fed rat model.
The male SD rats were divided into four group: blank group (B), fed with 50% corn starch + 10% sucrose diet ; control group (C), fed with high fructose diet alone ; treatment group 1 (T1), fed with high fructose diet plus red yeast rice, soybean, bitter melon, licorice and green algae; treatment group 2 (T2), fed with high fructose diet plus green algae, katsuobushi oligopeptide, catechin, and touchi extract. The study lasted for 13 weeks. Biochemical parameters related to blood pressure, fasting plasma glucose, insulin, triglyceride, total cholesterol, abdominal fat mass and the phosphorylation activity and expression of insulin signaling pathway related proteins were measured, and an oral glucose tolerance test (OGTT) was performed in this study.
The data shown that group C had significant increase in plasma triglyceride, cholesterol, LDL-C, hepatic total cholesterol and systolic blood pressure. Insulin sensitivity and HDL/TC ratio were decrease as compared to group B. Further evaluated the possible mechanism of high fructose diet induced metabolic defects, we found that the rats showed decreased phosphorylation activities of insulin receptor (IR) and Akt and total content of glucose transporter IV (Glut 4).
Compairing with group C, group T1 had higher HDL-C/TC ratio, and insulin sensitivity, and lower systolic blood pressure, triglyceride and abdominal fat mass. And the expressions of IR, insulin receptor substrates-1 (IRS-1), Akt and Glut 4 and phosphorylation activities of Akt were raised in T1 group.
Group T2 had lower systolic blood pressure, triglyceride and TC level as compared to group C. And the decreased insulin sensitivity was also ameliorated in group T2, which might result from the increased expressure of IR, Akt and Glut 4 and the increased phosphorylation activity of Akt.
The result showed that the combinatorial health food we used in this study may improve of metabolic syndrome effectively. Furthermore, the basal diet we used in the above was not the chow diet in common use. We designed anther study to investigate the influence of two diets on rats.
The male SD rats were divided into two group: experimental group (Co), fed with 50% corn starch + 10% sucrose diet ; control group (Ch), fed chow diet alone. The data shown that group Co had significant increase in plasma triglyceride, cholesterol, insulin, insulin and abdominal mass fat. And we suggested these phenomena induced by group Co may attribute to the contents of micro-mineral, sucrose and lipid.

目次
摘要.............................................I
ABSTRACT.......................................III
誌謝............................................Ⅴ
目錄............................................VI
表次............................................IX
圖次............................................Ⅹ
第壹章 前言.....................................1
第貳章 文獻回顧 .................................2
第一節 代謝症候群................................2
一、代謝症候群簡介 .................................2
二、代謝症候群的定義與診斷標準......................2
第二節 代謝症候群之致病機轉.........................6
一、胰島素阻抗....................................6
二、發炎因子......................................8
三、氧化壓力......................................9
四、肥胖.........................................9
第三節 代謝症候群的治療...........................10
一、生活型態.....................................10
二、藥物治療.....................................13
第五節 高果糖動物模式.............................16
一、果糖的影響...................................16
二、果糖代謝.....................................17
三、果糖與代謝症候群的產生 .......................17
第六節 食材介紹..................................18
一、甘草 .......................................18
二、紅麴 .......................................19
三、苦瓜 .......................................19
四、大豆 .......................................20
五、綠藻 .......................................21
五、兒茶素......................................21
六、豆豉 .......................................22
七、鰹魚 .......................................22
第参章 研究目的與實驗架構 .......................24
第一節 研究目的..................................24
第二節 實驗架構..................................26
第肆章 材料與方法..............................28
第一節 實驗材料..................................28
一、儀器設備.....................................28
二、實驗食材.....................................29
三、動物飼料.....................................29
四、化學藥品.....................................30
五、溶劑.........................................31
六、酵素套組.....................................32
七、抗體........................................32
八、其他........................................33
第二節 實驗方法..................................33
一、實驗動物.....................................33
二、動物分組與飼養 ...............................33
三、食材劑量選擇方法與詳細配方成分..................35
四、血壓之測量...................................42
五、採集禁食狀態之血液............................42
七、動物犧牲與檢體之收集與分析.....................45
第三節 統計分析..................................53
第伍章 結果....................................54
實驗Ⅰ 食材改善代謝症候群試驗......................54
一、生長狀況.....................................54
二、飼養期之血壓變化..............................54
三、飼養期禁食狀態血漿分析.........................54
四、口服葡萄糖耐受性試驗...........................56
五、組織臟器重量..................................59
六、犧牲後禁食血液生化指標.........................59
七、肝臟三酸甘油酯、膽固醇及TBARS分析..............60
八、脂肪組織胰島素訊息傳遞相關蛋白質表現量及磷酸化程度...........60
實驗Ⅱ 空白組比較試驗.............................62
一、生長狀況.....................................62
二、飼養期之血壓變化..............................62
三、飼養期禁食狀態血漿分析.........................62
四、口服葡萄糖耐受性試驗...........................63
五、組織臟器重量..................................63
六、犧牲後禁食血液生化指標.........................64
七、肝臟三酸甘油酯及膽固醇分析.....................64
第陸章 討論....................................65
實驗Ⅰ食材改善代謝症候群試驗.......................65
一、生長狀態及組織臟器變化.........................65
二、胰島素敏感性與血糖............................66
三、血脂變化.....................................67
四、血壓變化.....................................68
五、胰島素訊息傳遞路徑相關蛋白表現量及活化量.........69
實驗Ⅱ 空白組比較試驗.............................70
第柒章 結論....................................71
第八章 參考文獻................................101



表次
表2-1、不同代謝症候群診斷標準之比較........................................................5
表2-2、代謝症候群患者生活型態的改變 .....................................................12
表4-1、各組飼料組成成份 .............................................................................37
表4-2、50%玉米澱粉飼料之組成...................................................................38
表4-3、Rodent Chow diet的組成.................................................................... 39
表4-4、Rodent Chow diet與 Harlan Teklad diet之礦物質組成....................40
表4-5、Rodent Chow diet與 Harlan Teklad diet之油質組成........................41
表5-1、大鼠於第4、8和12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扣除基礎值之變化量.........................93
表5-2、大鼠飲食處理13週後之組織臟器重.................................................94
表5-3、大鼠飲食處理13週後之禁食血漿葡萄糖、胰島素、三酸甘油酯
、膽固醇、高密度脂蛋白膽固醇、低密度脂蛋白膽固醇..………….95
表5-4、大鼠飲食處理13週後之肝臟三酸甘油酯、膽固醇與TBARS含
量.........................................................................................................96
表5-5、大鼠於第12週時進行口服葡萄糖耐受性試驗血漿葡萄糖和胰島
素濃度曲線下面積變化量.................................................................97
表5-6、大鼠飲食處理13週後之組織臟器重量.............................................98
表5-7、大鼠飲食處理13週後之禁食血漿葡萄糖、胰島素、三酸甘油酯
、膽固醇、高密度脂蛋白膽固醇與低密度脂蛋白膽固醇濃度.........99
表5-8、大鼠飲食處理13週後之肝臟三酸甘油酯與膽固醇含量…….......100



圖次
圖 2-1、胰島素訊息傳遞路徑…………………………………………………7
圖 2-2、PPARs之表現 ………………………………………………………16
圖 2-3、果糖在肝臟中的利用…………………………………………………17
圖5-1、大鼠飲食處理12週期間體重變化之情形………………………… 72
圖5-2、大鼠飲食處理12週期間(A)收縮壓(B)舒張壓變化之情形..………73
圖5-3、大鼠飲食處理12週期間禁食血漿葡萄糖變化之情形…………… 74
圖5-4、大鼠飲食處理12週期間禁食血漿胰島素變化之情形…………… 75
圖5-5、大鼠飲食處理12週期間禁食血漿三酸甘油酯變化之情形……… 76
圖5-6、大鼠飲食處理12週期間禁食血漿膽固醇變化之情形…………… 77
圖5-7、大鼠飲食處理12週期間禁食血漿(A)高密度脂蛋白膽固醇(B)
HDL - C/TC變化之情形 ……………………………………………78
圖5-8、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 ………………..……………………...… 79
圖5-9、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 ……………….….…………………….… 80
圖5-10、實驗12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 ………………..…………………...… 81
圖5-11、大鼠飲食處理13週後大鼠脂肪細胞中胰島素訊息傳遞相關蛋
白質表現量.........................................................................................82
圖5-12、大鼠飲食處理13週後脂肪細胞中訊息傳遞相關蛋白質表現量
之定量結果.........................................................................................83
圖5-13、大鼠飲食處理13週後脂肪細胞中訊息傳遞相關蛋白質活化量之定量結果.................................................................................................84
圖5-14、大鼠飲食處理12週期間體重變化之情形 ……………………… 85
圖5-15、大鼠飲食處理12週期間血壓變化之情形 ……………………… 86
圖5-16、大鼠飲食處理12週期間禁食血漿葡萄糖變化之情形………...…87
圖5-17、大鼠飲食處理12週期間禁食血漿胰島素變化之情形………...…88
圖5-18、大鼠飲食處理12週期間禁食血漿三酸甘油酯變化之情形…...…89
圖5-19、大鼠飲食處理12週期間禁食血漿膽固醇變化之情形………...…90
圖5-20、大鼠飲食處理12週期間禁食血漿(A)高密度脂蛋白膽固醇(B) HDL-C/TC變化之情形……………………..………………….… 91
圖5-21、實驗12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...………………..…………………… 92

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