臺灣博碩士論文加值系統

先前研究顯示，綠茶中多酚以EGCG生物活性為最高，具抗氧化之功效。本研究目的為探討指標成分為EGCG之多酚奶粉，對老化促進小鼠學習記憶能力及抗氧化狀態之影響。實驗以3月與6月齡雄性及雌性SAMP8 (senescence-accelerated mouse) 小鼠為對象，隨機分為對照組及實驗組，實驗組又分為給予1.04、2.08、5.20 mg多酚組，每組20隻。實驗為期12週，飼養期間紀錄其攝食量與體重變化，並於攝食第11週判定老化指數；在行為測試方面測其活動量，於攝食第12週以單次被動迴避試驗及主動迴避試驗評估其學習記憶能力。動物犧牲後，採血進行生化分析，取肝臟測定肝中抗氧化酵素含量，另取腦部做丙二醛試驗及病理切片以觀察類澱粉蛋白沉積情形。
結果顯示，實驗期間體重變化、攝食量及活動量於四組間無顯著差異。老化指數評估方面，無論在3、6月齡雄性或雌性小鼠，多酚組之老化指數總分皆顯著低於對照組 (p<0.05)，且隨著年齡增加，老化指數有增加的趨勢。學習記憶方面，主動迴避試驗結果顯示， 3、6月齡雄性及雌性小鼠之對照組皆比實驗組有顯著較高之逃脫反應次數(p<0.05) ，表示多酚組有較佳的學習記憶能力。另於單次被動迴避試驗中發現，3、6月齡雄性及雌性實驗組在學習記憶保留上顯著較對照組佳 (p<0.05)。血液生化分析，3、6月齡雄性及雌性小鼠各實驗組之三酸甘油酯及總膽固醇濃度與對照組相比皆顯著降低 (p<0.05)。體內抗氧化防禦系統方面，3、6月齡雄性及雌性小鼠各實驗組之腦部MDA含量及肝臟蛋白質羰基濃度與對照組相比皆顯著降低 (p<0.05)。於肝臟超氧歧化酶、觸酶活性、麩胱苷肽過氧化酶、總含硫化合物及血液葡萄糖-6-磷酸去氫酶方面，不論在3、6月齡雄性及雌性小鼠，多酚組顯著高於對照組 (p<0.05)。在腦部β類澱粉蛋白沉積方面，3、6月齡雄性及雄性小鼠皆以多酚組顯著較對照組低 (p<0.05)。
綜合以上結果，長期於飼料中添加指標成分為EGCG之多酚奶粉，可提升老化促進小鼠體內抗氧化防禦系統之能力，減少腦部β-類澱粉蛋白沉積，進而達到增進學習記憶的能力。

Previous studies indicated that EGCG is the major and most active component of green tea catechins, and it acts as an antioxidant in the biological system. The purpose of our study was to investigate the effects of polyphenol-rich milk powder composed mainly of EGCG on learning and memory ability, and antioxidant status in 3 and 6-month-old senescence accelerated mice (SAMP8). SAMP8 mice were devised to four groups: control, 1.04 mg, 2.08 mg and 5.20 mg polyphenol (PP). Each group was consisted of twenty male and female mice. During feeding period, intake amount, body weight measurement and aging scores were recorded. Locomotion was recorded in evaluation of behavior; and single-trail passive avoidance test and active shuttle avoidance test in evaluation of learning and memory abilities. After the experiment, the mice were sacrificed to analyze the biochemical parameters, the antioxidant ability of serum, liver and brain, and the histopathological examination of brain were also observed and evaluated.
Our results showed that there was no significant difference in the body weight, food intake, and locomotion among four groups in 3 and 6-month-old mice. The aging score were increased with age, and the score of control groups were higher than the experimental groups in both male and female 3 and 6-month-old mice (p<0.05). The experimental groups had better active shuttle avoidance response in both male and female 3 and 6-month-old mice (p<0.05). 3 and 6-month-old male and female mice fed with polyphenol had significantly better single-trial passive avoidance results (p<0.05). 3 and 6-month-old male and female mice fed with polyphenol experiment diet had significantly lower triglycerol, total cholesterol than control group (p<0.05). Hepatic protein carbonyl levels, and malondialdehyde concentration and Aβ deposition of brain were significant lower in the experimental groups than in control ones in 3 and 6-month-old male and female mice. Polyphenol also brought about an augmentation in the activities of enzymic antioxidants in the liver, such as superoxide dismutase, catalase, glutathione peroxidase and total thiol levels, and increased the activity of glucose-6-phosphate dehydrogenase in the blood.
In summary, we conclude that the consumption of polyphenol-rich milk powder composed mainly of EGCG may improve the learning and memory ability of SAMP8 mice. And it may due to the mediation by EGCG promoting the antioxidative ability and reducing the brain pathological changed that lower the oxidative injury.

目 錄
頁次
中文摘要……….………..……………………………………………………Ⅰ
英文摘要……….…. …………………………………………………………III
目錄…..…………. ……….…………………………………………..………Ⅵ
表目錄………………….....…………………………..………………..……..X
圖目錄…………………...……………………………………………….…XII

第一章 前言……………………………………………..……………………1
第二章 文獻回顧……………………………………………………………..4
第一節 自由基與抗氧化防禦系統……………....…………………..…..4
壹、自由基與氧化壓力.…..……….…...………..……….……..4
貳、抗氧化防禦系統……………...…...………………………..5
一、酵素型抗氧化系統.…….…...………………………..5
二、非酵素型抗氧化系統……...…..……………………..7
第二節 老化…...……………………...…..……………..………………11
壹、老化之定義……. ...…...…………………………..………11
貳、老化的原因..……..…...………………………………..….11
參、老化與抗氧化…...…...……..……………………….……..12
肆、老年失智症……...…...…....….…………….……………..13
第三節 老化促進小鼠..…………..…...…..…..………………………...15
壹、老化促進小鼠…………...……...…………………………15
貳、老化促進小鼠之老化及病理特徵... ……..…....…………15
參、老化促進小鼠與學習記憶..…….. ..…….…….….…...….16
肆、老化指數系統………………..……....………………...….16
第四節 綠茶多酚…...………..……............……..………………...……21
壹、茶之簡介……....…………………..………….….….…….21
貳、綠茶之化學組成….…...........……..………………...…….22
參、綠茶多酚 (兒茶素類) 的代謝…...…………....……..…..26
肆、綠茶之生理功能...…..………………………....………….27
第五節 蘋果多酚……………….…..……………………………...……30
壹、蘋果之簡介…….…….....……………….……….….…….30
貳、蘋果中酚類化合物…..….…...……………………...…….30
參、蘋果多酚之生理功能..……….…...…………………..…..32
第六節 紅酒多酚…………....…..….……………………………...……33
壹、紅酒之簡介…………..……….…...………….….….…….33
貳、紅酒成分組成……….............…….………………...…….33
參、紅酒多酚之生理功能..……….……...………………..…..36

第三章 材料與方法………………………..…………………….…….…….37
第一節 實驗動物………..………………………………….….………..37
第二節 實驗材料…………………………………………....…………..37
第三節 實驗劑量………...……………………………….……………..39
第四節 實驗方法及步驟…...………………………….………………..41
壹、實驗流程…………………...……………...………………41
貳、老化指數判定………………...…….…..…………………43
參、活動量試驗………...............………….………….……….43
肆、學習記憶測試……………...………………………….…..45
一、主動迴避試驗…………..…...………………………45
二、單次被動迴避試驗…….……..………...……….…..47
伍、血液生化學分析……………..……..….…………………50
陸、腦部脂質過氧化物及肝臟抗氧化能力…..……..…...….50
一、丙二醛…….….………………………….………..50
二、超氧歧化酶….…….….....………………….……..53
三、麩胱苷肽過氧化酶..…....………….………..…….57
四、觸酶...………..……..….…..………………..…….58
五、蛋白質羰基…..….…...……………..…………..….60
六、總含硫化合物….………..…………………..…….62
柒、血液抗氧化能力分析.………..…………………………..64
捌、腦部病理切片觀察……..……..……………..………….65
第五節 統計分析...………….…………………………………..……….76
第四章 結果與討論…...………..…………………… ……………….……..77
第一節 體重及攝食量變化…........………....………………….………..77
第二節 活動量…………………………………………………….……..77
第三節 老化指數………………...………………………………………82
第四節 學習與記憶能力…………………....………………….………..88
壹、主動迴避試驗…………………...…………………………88
貳、單次被動迴避試驗…………………………………….…..92
第五節 器官重量…………...……………………………………………95
第六節 血液生化值分析………....………………………………….…..95
第七節 腦部脂質過氧化物與肝臟抗氧化能力………..……..………101
一、脂質過氧化物丙二醛……..……..............………………101
二、超氧歧化酶………………..…………….…………….…107
三、麩胱苷肽過氧化酶…….…..…………...…………….….111
四、觸酶…….……..……...…….....…...………………….….115
五、蛋白質羰基……………….............………………….…..118
六、總含硫化合物…………………...…..……………….…..123
第八節 血液抗氧化能力.……….…………….....…………………….127
第九節 腦部β類澱粉蛋白沉積………………….…………………...130
第五章 綜合討論…………..……...……………………………………..136
第六章 結論………………………...……………………………………..138
第七章 參考文獻……………………..…………………..……………..….139

















表 目 錄
頁次
表一、老化指數判定標準……….…………………..…………………….….18
表二、SAM之病理生物學表型…………………...…………………….........20
表三、紅葡萄酒中酚類物質的抗氧化能力..………….………...……..…….35
表四、實驗飼料組成………………………..…………...….…………..…….40
表五、3月及6月齡雄性SAMP8小鼠餵食不同飼料12週後體重及攝食量之變化…………….……….………………………………..…………..….78
表六、3月及6月齡雌性SAMP8小鼠餵食不同飼料12週後體重及攝食量之變化……………..……………………………………………..……..….79
表七、3月齡SAMP8系小鼠餵食不同飼料11週後之活動量.....................….80
表八、6月齡SAMP8系小鼠餵食不同飼料11週後之活動量……………......81
表九、3月齡雄性SAMP8系小鼠餵食不同飼料11週後之老化指數…........................................................................................................84
表十、3月齡雌性SAMP8系小鼠餵食不同飼料11週後之老化指數……………………………………………………………...…...….85
表十一、6月齡雄性SAMP8系小鼠餵食不同飼料11週後之老化指數……………………………………………….…………….…..….86
表十二、6月齡雌性SAMP8系小鼠餵食不同飼料11週後之老化指數…………………………………………………………….…..….87
表十三、3及6月齡雄性SAMP8系小鼠餵食不同飼料12週後之器官重…………………………………………….…………….……..….97
表十四、3及6月齡雌性SAMP8系小鼠餵食不同飼料12週後之器官重……………………………………….…..……………….…..….98
表十五、3及6月齡雄性SAMP8系小鼠餵食不同飼料12週後血液生化值之比較………………………………...……………………….……..….99
表十六、3及6月齡雌性SAMP8系小鼠餵食不同飼料12週後血液生化值之比較………………………………………...………………….…..….100
表十七、3、6月齡雄性SAMP8小鼠餵食不同飼料12週後其腦部β-類澱粉蛋白沉積之比較…………………………..………………….…..….132
表十八、3、6月齡雌性SAMP8小鼠餵食不同飼料12週後其腦部β-類澱粉蛋白沉積之比較……………………………...…………………...….133












圖 目 錄
頁次
圖一、體內抗氧化防禦系統…………...……….…………………………..10
圖二、兒茶素類化學結構與分類…………….……………………………..25
圖三、ECG之抗氧化反應機制………………………………..…….……27
圖四、蘋果多酚種類……………………….…………………………..……31
圖五、實驗流程圖……….………………………………………….….…….42
圖六、活動量裝置…………………………………….…….………..………44
圖七、主動迴避試驗裝置圖……………………………….…………..…….49
圖八、被動迴避試驗裝置圖………………………………..…………..……49
圖九、病理組織切片流程圖…………………………………………...…….74
圖十、腦部Ｆ區域切面圖…………………………………………...…….75
圖十一、3、6月齡雄性SAMP8系小鼠餵食不同飼料12週後經主動迴避試驗之逃脫反應次數………………………….……………….….………90
圖十二、3、6月齡雌性SAMP8系小鼠餵食不同飼料12週後經主動迴避試驗之逃脫反應次數…………………………………………..……..…91
圖十三、3、6月齡雄性SAMP8系小鼠餵食不同飼料12週後經單次被動迴避試驗之滯留時間………………………………………………...……93
圖十四、3、6月齡雌性SAMP8系小鼠餵食不同飼料12週後經單次被動迴避試驗之滯留時間……………………………………………..………94
圖十五、3月及6月齡雄性SAMP8系小鼠餵食不同飼料12週後之腦部丙二醛濃度…………………………………………………………………104
圖十六、3月及6月齡雌性SAMP8系小鼠餵食不同飼料12週後之腦部丙二醛濃度………………………………………………………….………105
圖十七、比較3月及6月齡雄、雌性SAMP8系小鼠餵食不同飼料12週後之腦部丙二醛濃度……………………………………………….………106
圖十八、3月及6月齡雄性SAMP8系小鼠餵食不同飼料12週後之肝臟超氧歧化酶活性……………………………………………………….……109
圖十九、3月及6月齡雌性SAMP8系小鼠餵食不同飼料12週後之肝臟超氧歧化酶活性………………………………………………………….…110
圖二十、3月及6月齡雄性SAMP8系小鼠餵食不同飼料12週後之肝臟麩胱苷肽過氧化酶活性…………………………………………….………113
圖二十一、3月及6月齡雌性SAMP8系小鼠餵食不同飼料12週後之肝臟麩胱苷肽過氧化酶活性…………………………………………….……114
圖二十二、3月及6月齡雄性SAMP8系小鼠餵食不同飼料12週後之肝臟觸酶活性…………………………………………………………………116
圖二十三、3月及6月齡雌性SAMP8系小鼠餵食不同飼料12週後之肝臟觸酶活性………………………………………………………………….117
圖二十四、3月及6月齡雄性SAMP8系小鼠餵食不同飼料12週後之肝臟蛋白質羰基濃度…………………………………………………..……120
圖二十五、3月及6月齡雌性SAMP8系小鼠餵食不同飼料12週後之肝臟蛋白質羰基濃度……………………………………………………….…121
圖二十六、比較3月及6月齡雄、雌性SAMP8系小鼠餵食不同飼料12週後之肝臟蛋白質羰基濃度……………………………………….………122
圖二十七、3月及6月齡雄性SAMP8系小鼠餵食不同飼料12週後之肝臟總含硫化合物之濃度……………………………………………….……124
圖二十八、3月及6月齡雌性SAMP8系小鼠餵食不同飼料12週後之肝臟總含硫化合物之濃度………………………………………………..…125
圖二十九、比較3月及6月齡雄、雌性SAMP8系小鼠餵食不同飼料12週後之肝臟總含硫化合物之濃度…………………………………….……126
圖三十、3月及6月齡雄性SAMP8系小鼠餵食不同飼料12週後之血液葡萄糖-6-磷酸去氫酶……………………………………………….…...…128
圖三十一、3月及6月齡雌性SAMP8系小鼠餵食不同飼料12週後之血液葡萄糖-6-磷酸去氫酶…………………………...………………….……129
圖三十二、SAMP8小鼠腦部β-類澱粉蛋白沉積形成……..………….…...…134
圖三十三、對照組SAMP8小鼠腦部β-類澱粉蛋白沉積情形.……….…...…135
圖三十四、實驗組SAMP8小鼠腦部β-類澱粉蛋白沉積情形…...………...…135

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