臺灣博碩士論文加值系統

現代飲食與生活習慣使罹患糖尿病的人口增加，糖尿病已成為全球主要的健康問題之一。先前研究指出石花菜熱水萃物 (Gelidium amansii hot water extract, GHE)，可有效降低血脂及肝臟脂質濃度，增加糞便三酸甘油酯及膽酸的排泄，活化脂解作用相關酵素及蛋白表現，抑制脂肪合成作用，但未有文獻深入探討石花菜熱水萃取物對其糖代謝的影響，為了探討探討石花菜熱水萃物對於糖尿病糖代謝之影響，本研究實驗一以雄性Sprague Dawley (SD) 大白鼠進行為期八週的實驗，以50 mg/kg BW streptozotocin (STZ) 誘導，模擬第一型糖尿病，共分為三組 (1) 正常控制組 (Normal control, NC) (2) 糖尿病組 (Diabetes Mellitus in high fat diet, DM) (3) 石花菜熱水萃組 (DM in high fat diet + Gelidium amansii hot-water extract, DG)，結果顯示，對於大白鼠，GHE無法降低血糖，但可顯著降低糖尿病引起的高尿糖，推測可能是此誘導方式致使血糖過高，導致GHE無法發揮作用，因此進行實驗二，使用不同的誘導方式，以230 mg/kg BW nicotinamide (NA) 與65 mg/kg BWSTZ誘導，模擬第二型糖尿病，共分為四組 (1) 正常控制組 (Normal control, NC) (2) 糖尿病組 (DM in high fat diet, DM) (3) 石花菜熱水萃組 (DM in high fat diet + Gelidium amansii hot-water extract, DG) (4) 藥物正控制組 (DM in high fat diet + Rosiglitazone, DR)，結果發現，GHE對糖尿病大白鼠之葡萄糖耐受性試驗以及胰島素耐受性試驗，雖無明顯改善效果，但GHE可以減少糖尿病大白鼠肝臟的脂質濃度，並且增加脂解酵素hormone sensitive lipase (HSL) 活性，減少脂肪組織的堆積，GHE可顯著降低肝臟glucose-6-phosphatase的酵素活性，顯著增加肝臟肝醣濃度，並降低小腸內maltase酵素活性。綜合上述，GHE雖然無法降低血糖，但可減少肝臟的糖質新生、增加肝醣合成作用以及降低小腸雙醣酶活性，因此可顯著於改善糖尿病大白鼠之糖代謝。

Previous studies have pointed out that Gelidium amansii hot water extract (GHE) can effectively reduce plasma lipids and liver lipids concentrations, increase the excretion of fecal triglycerides and bile acid, ameliorated lipolysis enzymes and protein levels, inhibit of lipids synthesis, but there is no research discussing the effect of GHE on sugar metabolism. In order to investigate the effect of GHE on glucose metabolism in diabetic rats. Experiment 1: Male Sprague-Dawley (SD) rats were induced by 50 mg/kg BW streptozotocin (STZ), which represents type 1 DM and they were divided into 3 groups: (1) Normal control (NC) (2) Diabetic rats in high fat diet (DM) (3) DM + Gelidium amansii hot-water extract (DG). All the rat were fed the experimental diets and drinking water ad libitun for 8 weeks. The results showed that GHE could not decrease plasma glucose, but significantly decrease the high urine glucose caused by diabetes. Therefore, in experiment 2, a different induction method was used to induce hyperglycemia in rats with nicotinamide (NA) and STZ. Male Sprague-Dawley (SD) rats were induced by 230 mg/kg BW NA and 65 mg/kg BW streptozotocin, which represents type 2 DM and were divided into 4 groups: (1) Normal control (NC) (2) Diabetic rats in high fat diet (DM) (3) DM + Gelidium amansii hot-water extract (DG). (4) NA and STZ induced DM in high fat diet + Rosiglitazone, (DR), Rats were fed with experimental diets and drinking water ad libitun for 10 weeks. The results showed that GHE did not significantly improve the glucose tolerance test and insulin tolerance test of diabetic rats. However, GHE significantly reduced the lipid concentration in the liver. In adipose tissue, GHE was showed to increase hormone sensitive lipase (HSL) expression, which indicate that GHE reduced lipid accumulation by stimulating lipolysis, via elevation of HSL. GHE significantly reduced the enzyme activity of liver glucose-6-phosphatase, significantly increase the liver glycogen concentration, and reduce the activity of maltase in the small intestine. Base on the above result, GHE cannot reduce plasma glucose concentration, but it can reduce liver gluconeogenesis, increase glycogen synthesis and reduce the activity of disaccharidase in the small intestine. These results suggested that GHE might improve glucose metabolism in type 2 DM.

目錄
第壹章 前言 1
第貳章 文獻整理 2
第一節 石花菜 2
一、 海藻簡介 2
二、 Glidium amansii安曼司石花菜 2
三、 石花菜熱水萃物之結構與特性 3
四、 石花菜對糖代謝之影響 3
第二節 糖尿病 (Diabetes Mellitus) 4
一、 糖尿病簡介 4
二、 糖尿病診斷 4
三、 糖尿病分類 5
四、 誘導糖尿病動物模式 6
五、 糖代謝 (Carbohydrate metabolism) 10
第三節 糖代謝相關傳遞因子 12
一、 Protein kinase B (PKB / Akt) 12
二、 Glucose transporter (GLUT) 12
三、 Mitogen-activated protein kinase (MAPK) 12
四、 Phosphoenolpyruvate (PEPCK) 13
五、 AMPK-activated protein kinase (AMPK) 14
六、 Sodium glucose transport (SGLT) 15
第參章 實驗設計 16
第一節 實驗動機與目的 16
第二節 實驗流程: 16
⦾實驗一：以STZ誘導之糖尿病大白鼠 16
⦾實驗二：以NA與STZ誘導之糖尿病大白鼠 17
第三節 分析項目 18
⦾實驗一 18
⦾實驗二 18
第肆章 實驗材料 19
第一節 實驗動物 19
⦾實驗一 19
⦾實驗二 19
第二節 實驗飼料 19
第三節 實驗樣品 19
第四節 實驗儀器 20
第伍章 實驗方法 22
第一節 實驗分組 22
⦾實驗一 22
⦾實驗二 22
第二節 動物飼養 22
第三節 樣品收集 22
第四節 飼料配方 23
⦾實驗一 23
⦾實驗二 24
第五節 樣品分析 25
一、 血漿分析 25
二、 肝臟分析 28
三、 小腸分析 32
四、 脂肪組織分析 32
五、 糞便分析 33
六、 尿液分析 34
七、 體重、攝食量、飲水量、排尿量 34
八、 統計分析 34
第陸章 結果 35
⦾實驗ㄧ 35
第一節 誘導後空腹血糖之結果 35
第二節 實驗期間大白鼠體重、攝食量、飲水量、排尿量之變化 35
第三節 實驗結束犧牲時白鼠組織臟器重量之變化 35
第四節 犧牲後大白鼠血漿中各項指標之變化 35
第五節 犧牲後大白鼠肝臟中各項指標之變化 35
一、 肝臟中脂質含量之變化 35
二、 肝臟中肝醣之變化 36
三、 肝臟中TBARS之變化 36
第六節 大白鼠糞便重量與脂質含量之變化 36
第七節 大白鼠尿液中葡萄糖含量之變化 36
⦾實驗二 36
第ㄧ節 誘導後口服葡萄糖耐受性試驗之結果 36
第二節 實驗期間大白鼠進行口服葡萄糖耐受性試驗之變化 36
第三節 實驗期間大白鼠進行胰島素耐受性試驗之變化 36
第四節 實驗期間大白鼠體重、攝食量、食物利用率之變化 37
第五節 犧牲時白鼠組織臟器重量之變化 37
第六節 犧牲後大白鼠血漿中各項指標之變化 37
一、 血漿中葡萄糖與胰島素含量之變化 37
二、 血漿脂質含量之變化 37
三、 血漿AST、ALT、GLP-1之變化 37
第七節 犧牲後大白鼠肝臟中各項指標之變化 37
一、 肝臟中脂質含量之變化 37
二、 肝臟中肝醣濃度與糖代謝相關酵素之變化 38
三、 肝臟中脂質過氧化物之變化 38
第八節 犧牲後大白鼠脂肪中各項指標之變化 38
一、 脂肪中脂質含量之變化 38
二、 脂肪中脂解速率之變化 38
第九節 犧牲後大白鼠小腸中雙醣酶活性之變化 38
第十節 大白鼠糞便重量與脂質含量之變化 38
第柒章 討論 39
第ㄧ節 GHE對糖尿病大白鼠體重、攝食量、飲水量、排尿量與組織臟器重量之影響 39
⦾實驗一 39
⦾實驗二 39
第二節 GHE對糖尿病大白鼠糖代謝之影響 40
⦾實驗一 40
⦾實驗二 41
一、 血漿中血糖與胰島素相關數值之變化 41
二、 肝臟中糖代謝之變化 41
三、 小腸中雙醣酶之變化 42
第三節 GHE對糖尿病大白鼠血漿生化數值之影響 42
⦾實驗二 42
第四節 GHE對糖尿病大白鼠脂質代謝之影響 42
⦾實驗一 42
一、 血漿與脂肪組織中脂質代謝之變化 42
二、 肝臟中脂質代謝與脂質過氧化之變化 43
三、 糞便中脂質代謝之變化 43
⦾實驗二 43
一、 血漿中脂質代謝之變化 43
二、 肝臟中脂質代謝與脂質過氧化之變化 43
三、 脂質中脂質代謝之變化 44
四、 糞便中脂質代謝之變化 44
⦾羅格列酮 44
第五節 總論 45
第捌章 結論 46
第玖章 參考文獻 47


圖目錄
圖一、 誘導一週後大白鼠進行空腹血糖測定之結果。 56
圖二、 給予不同飲食後，大白鼠體重之變化。 57
圖三、 給予不同飲食8週後，大白鼠肝醣濃度之影響。 58
圖四、 給予不同飲食8週後，大白鼠肝臟TBARS濃度之影響。 59
圖五、給予不同飲食8週後，大白鼠尿液中葡萄糖濃度之影響。 60
圖六、 誘導一週後大白鼠進行口服葡萄糖耐受性試驗之結果。 61
圖七、第9週大白鼠進行口服葡萄糖耐受性試驗之結果。 62
圖八、第9週大白鼠進行口服葡萄糖耐受性試驗曲線下面積之結果。 63
圖九、第10週大白鼠進行胰島素耐受性試驗之結果。 64
圖十、第10週大白鼠進行胰島素耐受性試驗曲線下面積之結果。 65
圖十一、 給予不同飲食後，大白鼠體重之變化。 66
圖十二、 給予不同飲食10週後，大白鼠血液GLP-1濃度之影響。 67
圖十三、 給予不同飲食10週後，大白鼠肝醣濃度之影響。 68
圖十四、 給予不同飲食10週後，大白鼠肝臟TBARS濃度之影響。 69
圖十五、 給予不同飲食10週後，大白鼠脂肪三酸甘油酯濃度之影響。 70
圖十六、 給予不同飲食10週後，大白鼠腎臟周圍脂肪HSL活性之影響。 71
圖十七、 給予不同飲食10週後，大白鼠小腸雙醣酶活性之影響。 72


表目錄
表一、給予不同飲食8週後，大白鼠體重、攝食量、飲水量、排尿量之影響。 73
表二、給予不同飲食8週後，大白鼠組織臟器重量之影響。 74
表三、給予不同飲食8週後，大白鼠肌肉重量之影響。 75
表四、給予不同飲食8週後，大白鼠脂肪組織重量之影響。 76
表五、給予不同飲食8週後，大白鼠血漿中相關數值之影響。 77
表六、給予不同飲食8週後，大白鼠肝臟中脂質含量之影響。 78
表七、給予不同飲食8週後，大白鼠糞便相關數值之影響。 79
表八、給予不同飲食9週後，大白鼠在口服葡萄糖耐受性試驗之血糖變化。 80
表九、給予不同飲食10週後，大白鼠在胰島素耐受性試驗之血糖變化。 81
表十、給予不同飲食10週後，大白鼠體重、攝食量之影響。 82
表十一、給予不同飲食10週後，大白鼠組織臟器重量之影響。 83
表十二、給予不同飲食10週後，大白鼠肌肉重量之影響。 84
表十三、給予不同10週後，大白鼠脂肪組織重量之影響。 85
表十四、給予不同飲食10週後，大白鼠血漿中血糖、胰島素濃度之影響。 86
表十五、給予不同飲10週後，大白鼠血漿中脂質相關數值之影響。 87
表十六、給予不同飲食10週後，大白鼠血漿中AST、ALT指標之影響。 88
表十七、給予不同飲食10週後，大白鼠肝臟中脂質含量之影響。 89
表十八、給予不同飲食10週後，大白鼠肝臟相關酵素活性之影響。 90
表十九、給予不同飲食10週後，大白鼠糞便重量、脂質含量之影響。 91

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