臺灣博碩士論文加值系統

豆粕由於蛋白質含量高、價廉且供應穩定, 為重要蛋白質供應者，已知去醣基大豆異黃酮及胜肽具抗肥胖活性。本研究分別以 Lactobacillus sp. FPS 2520 及 Bacillus sp. N1菌株進行單株及混合菌株液態發酵豆粕，探討發酵豆粕產品之抗肥胖活性。以五週齡 Sprague-Dawley 大鼠，隨機分為 9 組：(1) Normal diet 組 (ND)，其餘八組以高脂飼料誘導肥胖分為 (2) High-Fat diet 控制組 (HFD)，(3) HFD + 未發酵豆粕 1000 mg/kg 組 (SM 1000)，(4) 和 (5) HFD + FPS 2520 發酵產品，劑量分別為 500、1000 mg/kg 組 (FPS 500、FPS 1000)，(6) 和 (7) HFD + N1 發酵產品，劑量分別為 500、1000 mg/kg 組 (N1 500、N1 1000)，(8) 和 (9) HFD + 複合菌株發酵產品，劑量分別為 500、1000 mg/kg 組 (Mix 500、Mix 1000)，SD 大鼠經十週高脂飼料誘導肥胖後，餵食各測試樣品六週，顯示各實驗組除了 SM 1000 組外，體重均顯著低於HFD組，尤以 Mix 1000 組下降最大，與 ND 組相近。大鼠腹部及副睪脂肪含量變化亦和體重變化相似且具劑量依賴性，Mix 1000 組之腹部及副睪脂肪量分別比 HFD 組下降 47.7% 及 41.1%。各測試發酵產物均顯著降低血漿中三酸甘油脂及總膽固醇含量，Mix 1000 組比HFD 組下降 11.1% 及 29.8%。各測試發酵產物均降低血漿中 Alanine aminotransferase (ALT)、Aspartate aminotransferase (AST) 及 Creatinine 濃度。此外，各式菌株發酵產物均可降低脂肪酸合成酶 (FAS)、乙醯輔酶 A 羧化酶 (ACC) 酵素活性及增加荷爾蒙敏感性脂解酶 (HSL)、脂蛋白脂肪酶 (LPL) 酵素活性，且均以 Mix 1000 組的效果最大。綜合上述，由 FPS 2520 及 N1單株或複合菌株發酵所得豆粕均具降低脂質累積能力之抗肥胖活性，其中尤以複合菌株發酵的效果最顯著。

Because of its high protein content, low cost and stable supply, soybean meal (SBM) is an important protein source. It is known that deglycosyl soy isoflavones and peptides have anti-obesity activity. In this study, the single strain or mixed strains of Lactobacillus sp. FPS 2520 and Bacillus sp. N1 were used to ferment SBM, and the anti-obesity activity of the fermented SBM products were investigated using a high fat-induced animal model. Five-week-old Sprague-Dawley rats were randomly divided into 9 groups: (1) Normal diet group (ND), and the remaining 8 groups were divided into high-fat diet-induced obesity including (2) High-Fat diet control group (HFD), ( 3) HFD + unfermented soybean meal 1000 mg/kg group (SM 1000), (4) & (5) HFD + FPS 2520 fermented products at dosage of 500 and 1000 mg/kg, respectively, (FPS 500, FPS 1000), (6) & (7) HFD + N1 fermented products at dosage of 500 and 1000 mg/kg, respectively, (N1 500, N1 1000), (8) & (9) HFD + mixed strain fermented products at dosage of 500 and 1000 mg/kg, respectively, (Mix 500, Mix 1000), SD rats were successfully induced to become obesity after 10 weeks of induction by high fat diet, and then, the various tested fermented products were orally ingested by 6 weeks. Except the SM 1000 group, the body weight gains for the rest experimental groups were significantly lower than that of HFD group, among which Mix 1000 group being the lowest, with 25.8% reduction, compared to that of HFD. The changes for abdominal fat weight and epididymis fat weight were also similar to that of body weight gain, with Mix 1000 group being lowest, with 47.7% and 41.1% reduction, respectively, compared to those of HFD. All the tested fermented products significantly reduced the levels of plasma triglyceride and total cholesterol with 11.1% and 29.8% reduction were obtained for Mix 1000 group, compared to HFD group. Similarly, the plasma alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and creatinine levels were decreased for all experimented groups. The activity of fatty acid synthase (FAS) and acetyl CoA carboxylase (ACC) in liver were significantly decreased, and the activity of hormone sensitive lipase (HSL) and lipoprotein lipase (LPL) in adipose tissue were significantly decreased, for the groups fed with fermented SBM, with Mix 1000 group being most. In summary, the fermented SBM by either FPS 2520 or N1 were demonstrated to have anti-obesity activity, with mix strain fermented SBM being the most.

目錄
壹、前言 2
貳、文獻回顧 3
1. 肥胖 3
1-1.肥胖的成因 3
1-2.脂肪組織與肥胖 4
1-3.脂質與人體間之關係 5
1-4.肥胖者體內代謝異常之情況 5
1-5.脂肪組織中脂質代謝相關酵素 6
1-5-1. 荷爾蒙敏感性脂解酶 (Hormone-sensitive lipase, HSL) 6
1-5-2. 脂蛋白脂解酶 (Lipoprotein lipase, LPL) 6
1-6.肥胖者易罹患的疾病與其死亡率 7
2. 黃豆與豆粕 8
3. 黃豆和黃豆食品中之化學成分 9
參、實驗設計 12
肆、實驗材料與方法 14
一、 實驗材料 14
1. 原料 14
2. 實驗菌株 14
3. 化學藥品 14
4. 實驗動物 14
5. 實驗動物飼料 14
6. 動物實驗試劑套組 15
7. 動物組織切片 15
二、 儀器設備 15
三、 實驗方法 16
1. 菌種保存 16
2. 菌種活化 17
3. 樣品製備與分析 17
3-1. Lactobacillus sp. FPS 2520單株發酵 17
3-2. Bacillus sp. N1單株發酵 17
3-3. 複合菌株發酵 17
3-4. 異黃酮萃取 17
3-5. 異黃酮分析 18
4. 動物飼養與分組 18
5. 動物犧牲與取樣分析 19
5-1. 血液分析 19
5-1-1. 血漿中葡萄糖濃度測定 19
5-1-2. 血漿中總膽固醇濃度測定 19
5-1-3. 血漿中三酸甘油酯濃度測定 20
5-1-4. 血漿中脂蛋白 (Lipoprotein) 分離與含量測定 20
5-1-5. 血漿蛋白濃度測定 21
5-1-6. 血漿中胰島素含量測定 21
5-1-7. 血漿中 2-thiobarbituric acid reactive substances (TBARS) 含量測定 22
5-1-8. 血漿中天門冬氨酸胺基轉胺酶 (Aspartate aminotransferase, AST) 及丙氨酸胺基轉胺酶 (Alanine aminotransferase, ALT) 活性測定 23
5-2. 肝臟分析 24
5-2-1. 肝臟脂質萃取 24
5-2-2. 肝臟總膽固醇及三酸甘油酯含量測定 25
5-2-3. 肝臟中 2-thiobarbituric acid reactive substances (TBARS) 含量測定 25
5-2-4. 肝臟酵素活性測定 25
5-3. 脂肪分析 28
5-3-1. 脂肪細胞質液製備 28
5-3-2. 荷爾蒙敏感性脂解酶 (Hormone sensitivity lipase, HSL) 含量測定 28
5-3-3. 脂蛋白脂解酶 (Lipoprotein lipase, LPL) 含量測定 30
5-4. 組織病理學切片 31
5-4-1. 組織切片之固定 31
5-4-2. 組織脫水及石蠟包埋 31
5-4-3. 石蠟切片 31
5-4-4. 切片染色 31
6. 統計分析 32
伍、結果與討論 33
一、口服葡萄糖耐受性試驗 (Oral glucose tolerance test, OGTT) 33
1. 大鼠餵食不同飼料六週後口服葡萄糖耐受性測試之血糖變化 33
二、大鼠攝食量、飲水量、體重及組織臟器重量變化 34
1. 實驗期間攝食量及飲水量變化情形 34
2. 實驗犧牲前後大鼠外觀變化情形 34
3. 實驗期間各週體重及體重變化量 35
4. 大鼠組織臟器重量及脂肪重量變化 36
三、大鼠血漿生化指標 37
1. 給予不同實驗樣品六週後大鼠犧牲之血糖相關參數 37
2. 給予不同實驗樣品六週後大鼠犧牲之血脂相關參數 38
3. 給予不同實驗飼料六週後大鼠犧牲血漿之脂質過氧化物數值 38
4. 給予不同實驗飼料六週後大鼠肝腎功能之評估 39
四、大鼠肝臟生化指標 40
1. 給予不同實驗飼料六週後大鼠犧牲之肝臟脂質相關參數 40
2. 給予不同實驗飼料六週後大鼠犧牲肝臟之脂質過氧化物數值 40
3. 給予不同實驗飼料六週後大鼠肝臟脂質代謝酵素分析 41
五、大鼠脂肪組織酵素分析 42
六、大鼠肝臟組織病理學切片 42
陸、結論 44
柒、參考文獻 45

 
圖目錄
圖一、大鼠攝取不同實驗飼料六週之口服葡萄糖耐受性試驗血糖變化。 55
圖二、試驗期間大鼠攝取不同飼料之每週平均攝食量。 59
圖三、試驗期間大鼠攝取不同飼料之每週平均飲水量。 60
圖四、攝取不同樣品六週後之大鼠外型 (A) 及腹部脂肪組織圖 (B)。 61
圖五、試驗期間大鼠體重變化。 62
圖六、大鼠起始、最終體重及體重增加量。 63
圖七、大鼠攝取不同實驗飼料六週之組織臟器重量。 64
圖八、大鼠攝取不同實驗飼料六週之組織臟器重量。 65
圖九、大鼠攝取不同實驗飼料六週之脂肪組織重量。 66
圖十、大鼠攝取不同實驗飼料六週之脂肪組織重量。 67
圖十一、肥胖大鼠餵食含樣品之飼料六週後之血糖含量。 68
圖十二、肥胖大鼠餵食含樣品之飼料六週後之胰島素含量。 69
圖十三、肥胖大鼠餵食含樣品之飼料六週後之血漿三酸甘油酯、總膽固醇及脂蛋白膽固醇含量。 70
圖十四、肥胖大鼠餵食含樣品之飼料六週後之血漿脂質過氧化數值。 71
圖十五、大鼠攝取不同飼料六週之血漿 AST 含量。 72
圖十六、大鼠攝取不同飼料六週之血漿 ALT 含量。 73
圖十七、大鼠攝取不同飼料六週之血漿 CREATININE 含量。 74
圖十八、大鼠攝取不同飼料六週之血漿 URIC ACID 含量。 75
圖十九、肥胖大鼠餵食含樣品之飼料六週後之肝臟三酸甘油酯、總膽固醇含量。 76
圖二十、肥胖大鼠餵食含樣品之飼料六週後之肝臟脂質過氧化數值。 77
圖二十一、肥胖大鼠餵食含樣品之飼料六週後之肝臟脂肪酸合成酶含量。 78
圖二十二、肥胖大鼠餵食含樣品之飼料六週後之肝臟乙醯輔酶 A 羧化酶含量。 79
圖二十三、肥胖大鼠餵食含樣品之飼料六週後腹部脂肪組織荷爾蒙敏感脂解酶含量。 80
圖二十四、肥胖大鼠餵食含樣品之飼料六週後腹部脂肪組織脂蛋白脂肪酶含量。 81
圖二十五、肥胖大鼠餵食含樣品之飼料六週後以 H&E 染色觀察肝臟組織切片(10X×20X)。 82



 
表目錄
表一、實驗飼料組成 (%)。 83

附錄
附錄一、異黃酮標準品 (A)、未發酵豆粕液 (B)、以 LACTOBACILLUS SP. FPS 2520 發酵豆粕懸浮液 24 小時 (C)、72 小時 (F)、以 BACILLUS SP. N1發酵豆粕懸浮液 24 小時 (D)、72 小時 (G)、複合菌株發酵豆粕懸浮液 24 小時 (E)、72 小時 (H) 異黃酮含量之 HPLC 圖譜。 84
附錄二、以不同菌株發酵豆粕懸浮液 72 小時之游離胺基態氮、總胜肽及異黃酮含量變化。 85
附錄三、實驗飼料礦物質組成。 86
附錄四、實驗飼料維生素組成。 87
附錄五、大鼠攝取不同實驗飼料六週之組織臟器及脂肪組織重量。 88
附錄六、肥胖大鼠餵食含樣品之飼料六週後之血漿三酸甘油酯、總膽固醇、脂蛋白膽固醇含量及脂質過氧化數值。 89
附錄七、肥胖大鼠餵食含樣品之飼料六週後之血漿 AST、ALT、肌酸酐及尿酸含量。 90
附錄八、肥胖大鼠餵食含樣品之飼料六週後之肝臟三酸甘油酯、總膽固醇含量及脂質過氧化數值。 91
附錄九、肥胖大鼠餵食含樣品之飼料六週後之肝臟脂肪酸合成酶及乙醯輔酶 A 羧化酶含量。 92
附錄十、肥胖大鼠餵食含樣品之飼料六週後腹部脂肪組織荷爾蒙敏感脂解酶及脂蛋白脂肪酶含量。 93

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