臺灣博碩士論文加值系統

心血管疾病為全球主要的死因之ㄧ，其與動脈粥狀硬化關係密切。研究指出當體內血脂與氧化壓力過高時，會導致低密度脂蛋白(LDL)之氧化，而其為動脈粥狀硬化之肇因。因此，降低血脂濃度與延緩LDL氧化有利於動脈粥狀硬化之預防及延緩。近年的研究主要著重於改善血脂濃度與補充外源性抗氧化劑，以達到延緩動脈粥狀硬化進程之效果。文獻指出巴西洋菇、黑豆及黃耆具有抗氧化或降血脂之功效；巴西洋菇的保健功效與黑豆、黃耆雖有所不同，但卻有互補功效，若以黑豆或黃耆為發酵基質之部分，生產巴西洋菇之發酵液，於發酵過程中可能使抗氧化活性成分被分解，成為較易被人體吸收形式並增加生物活性。
本研究以倉鼠為動物模式，探討巴西洋菇子實體、黑豆、黃耆以及以豆科植物為發酵基質之巴西洋菇發酵產物對血脂及低密度脂蛋白氧化之影響。論文主要進行三次動物試驗內容包括：(1)動物試驗I：實驗期分別為四週及八週，研究巴西洋菇子實體、黑豆、黃耆之抗動脈硬化能力。(2)動物試驗II：改善動物試驗I之缺失，再進行一次探討巴西洋菇子實體、黑豆、黃耆之抗動脈硬化能力。(3)動物試驗III：研究以豆科植物為發酵基質之巴西洋菇大量發酵產物之抗動脈硬化能力。
動物試驗I結果顯示，經攝食四週後，飼料中添加10%黑豆會使血中高密度脂蛋白膽固醇(HDL-C)濃度降低，且增加肝臟中膽固醇之濃度及肝重與相對副睪脂肪塊重；黃耆則會使血中低密度脂蛋白膽固醇(LDL-C)濃度下降。攝食八週後，飼料中添加10%黑豆或10%黃耆會增加肝臟中膽固醇之濃度；飼料中添加10%黑豆或10%巴西洋菇子實體則會使相對肝重增加。
動物試驗II結果顯示，添加10%黑豆與黃耆會增加血中HDL-C濃度與肝臟中膽固醇之濃度，而攝食黃耆則會使肝臟中脂質過氧化物含量減少；攝食含10%巴西洋菇子實體之飼料則會降低血中三酸甘油酯(TG)與極低密度脂蛋白膽固醇(VLDL-C)之濃度；在黑豆組、黃耆組與巴西洋菇組皆可使血中脂質過氧化物MDA的含量下降。
動物試驗III結果顯示，飼料中添加10%含黃豆為基質之巴西洋菇發酵產物GF4會使肝臟中脂質過氧化物、肝臟中膽固醇與TG含量以及血中脂質過氧化物MDA的含量下降；而含黑豆之巴西洋菇發酵產物GF3會使肝臟中膽固醇與血中脂質過氧化物MDA的含量減少；且此兩種巴西洋菇發酵產物皆使血中α-tocopherol濃度增加，顯示其可增加倉鼠體內的抗氧化活性，因此具有抗動脈粥狀硬化之潛力。

Cardiovascular disease is the main cause of death in the world and it is related to atherosclerosis. It was suggested that high blood lipid and oxidative stress would result in LDL oxidation leading to atherogenesis. Therefore, preventing or delaying the onset of atherosclerosis could start from lowering blood lipid and prolonging the lag phase of LDL oxidation. Recent studies were focused on improving blood lipid and replenishing exogenous antioxidants to delay the progression of atherosclerosis.
Scientific literatures reported that Agaricus blazei, black bean and Astragalus membranaceus showed antioxidative or hypolipidemic effects. The health protective effect of A. blazei was different from black bean and A. membranaceus, but they could complement one another. To use black bean or A. membranaceus as a part of the fermentation medium for the liquid fermentation of A. blazei, the active antioxidative compounds might be transformed into the more bioavailable form with higher biological activity.
Hamster was chosen as the animal model of this study to investigate the effects towards blood lipid and LDL oxidation of the fruiting body of A. blazei, black bean, A. membranaceus and the fermentation products of A. blazei-leguminous. Three animal experiments were conducted to examine the antiatherogenic effects. Animal study I was conducted for 4 weeks and 8 weeks, and the test materials were A. blazei fruiting bodies, black bean and A. membranaceus. Animal study II was conducted to correct the shortcomings of animal study I to proceed the experiment once again. Animal study III was conducted to examine the effects of the fermentation products of A. blazei-leguminous.
The results of animal study I showed that after feeding hamsters 4 weeks with 10% black bean, the hamsters had lower HDL-C in serum, higher hepatic cholesterol and their liver weight and relative fat pad weight increased. Adding 10% A. membranaceus in the test diet could decrease LDL-C in serum of hamsters after 4 weeks. Hamsters fed 8 weeks with 10% black bean and A. membranaceus had higher hepatic cholesterol. Adding 10% black bean or 10% A. blazei in the test diet increased their relative liver weight.
The results of animal study II showed that hamsters fed with 10% black bean or 10% A. membranaceus had higher serum HDL-C and hepatic cholesterol. A. membranaceus added at 10% level in the diet could also reduce thiobarbituric acid reactive substances (TBARS) in the liver. Hamsters fed with 10% A. blazei had lower triglyceride and VLDL-C in serum. Hamsters in Agaricus blazei fruiting bodies, black bean and A. membranaceus groups showed lower levels of serum MDA than high fat high cholesterol group.
The results of animal study III showed that hamsters fed with 10% fermentation product of A. blazei (GF4), which used soybean as a part of fermentation medium, had lower levels of serum MDA, liver TBARS, hepatic cholesterol and triglyceride. Hamsters fed with 10% fermentation product of A. blazei (GF3), which used black bean as a part of fermentation medium, had lower levels of hepatic cholesterol and serum MDA. Both fermentation products of A. blazei could raise the content of α-tocopherol in serum. It is evident from this study that the fermentation products of A. blazei show in vivo antioxidative activity and have the potential antiatherogenic ability.

摘要 .I
英文摘要 ..III
目錄 V
表次 .IX
圖次 . XI

壹、前言 1
貳、文獻回顧 2
一、高脂血症(Hyperlipidemia)、動脈粥狀硬化(atherosclerosis)與心血管疾病(cardiovascular disease) 2
(一) 脂蛋白 4
(二) 脂蛋白的代謝 6
(三) 膽固醇 7
(四) 動脈粥狀硬化 9
(五) 脂質與脂蛋白的氧化 14
(六) 抗氧化劑與動脈粥狀硬化之相關性 17
(七) 動脈粥狀硬化研究之動物模式 19
二、巴西洋菇 20
(一) 巴西洋菇之發現與由來 20
(二) 巴西洋菇之分類及型態特徵 20
(三) 巴西洋菇之組成與活性成分 21
(四) 巴西洋菇之安全性 23
(五) 巴西洋菇之生理活性 23
三、豆科植物-黑豆 25
(一) 黑豆簡介 25
(二) 黑豆之組成及食療效果 25
(三) 黑豆之生理活性 26
四、豆科植物-黃耆 28
(一) 黃耆之簡介 28
(二) 黃耆之生理活性 28
五、脂肪酸與血脂之相關性 30
(一) 單元不飽和脂肪酸 31
(二) 多元不飽和脂肪酸 31
六、具降血脂活性之物質 33
(一) 植物固醇 33
(二) 大豆異黃酮 35
(三) Probucol 37
參、研究目的與實驗架構 38
一、研究目的 38
二、實驗架構 40
肆、實驗材料與方法 43
一、實驗材料 43
二、化學藥品與溶劑 44
三、酵素套組與電泳膠片 46
四、動物飼料組成 46
五、儀器設備 47
(一) 用於原料前處理 47
(二) 用於原料之基本成分分析 47
(三) 用於動物飼料之配製 48
(四) 用於動物實驗樣品之分析 48
(五) 用於抗氧化成分(tocopherol)分析 49
六、實驗方法 49
(一) 一般成分分析 49
1. 水分 49
2. 粗蛋白 49
3. 粗脂肪 50
4. 灰份 51
5. 膳食纖維 51
6. 碳水化合物總量 53
七、動物試驗 53
(一) 動物試驗I 53
1. 動物飼養 53
2. 動物分組 53
(二) 動物試驗II 55
1. 動物飼養 55
2. 動物分組 55
(三) 動物試驗III 56
1. 動物飼養 56
2. 動物分組 57
(四) 樣本收集與處理 58
1. 血清 58
2. 肝臟 58
3. 副睪上之脂肪組織 59
(五) 生化分析項目 59
1. 血清脂質分析 59
2. 肝臟脂質分析 61
3. 體內抗氧化能力分析 62
八、統計分析 65
伍、結果與討論 70
一、試驗原料一般成分分析結果 70
二、動物實驗結果 74
(一) 動物試驗I 74
1. 動物體重、相對肝重及相對副睪脂肪塊重之變化 70
(1)實驗期四週 74
(2)實驗期八週 75
2. 血清三酸甘油酯、總膽固醇與各種脂蛋白膽固醇濃度之變化 79
(1)實驗期四週 79
(2)實驗期八週 79
3. 肝臟TBARS、膽固醇及三酸甘油酯含量之變化 80
(1)實驗期四週 80
(2)實驗期八週 81
4. 分離脂蛋白的效果 87
(1)實驗期四週 87
(2)實驗期八週 87
5. 銅離子誘導LDL氧化之lag phase值 87
(1)實驗期四週 87
(2)實驗期八週 88
(二) 動物試驗II 93
1. 動物體重變化、相對肝重及相對副睪脂肪塊重與組織臟器重 94
2. 血清三酸甘油酯、總膽固醇、各種脂蛋白膽固醇濃度之變化 94
3. 銅離子誘導LDL氧化之lag phase值 96
4. 血清中MDA含量之變化 98
5. 肝臟TBARS、膽固醇及三酸甘油酯含量之變化 101
6. 分離脂蛋白的效果 102
7. 血中α-tocopherol含量之變化 102
(三) 動物試驗III 108
1. 動物體重變化、相對肝重及相對副睪脂肪塊重與組織臟器重 108
2. 血清三酸甘油酯、總膽固醇、各種脂蛋白膽固醇濃度之變化 110
3. 銅離子誘導LDL氧化之lag phase值 111
4. 血清中MDA含量之變化 112
5. 肝臟TBARS、膽固醇、三酸甘油酯含量之變化 113
6. 分離脂蛋白的效果 114
7. 血清中α-tocopherol含量之變化 115
陸、結論 123
柒、參考文獻 124
捌、附錄 142

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