臺灣博碩士論文加值系統

研究指出，兒茶素(catechins)具有抗氧化、降血糖之功能。本研究目的在探討兒茶素對老化促進小鼠學習記憶、體內抗氧化狀態、血糖及胰島素之影響。實驗以3月齡與6月齡雄性及雌性老化促進小鼠(senescence accelerated mice,SAMP8)為對象，分為對照組、實驗組(50, 200, 800 ppm兒茶素水溶液) ，為期12週。實驗期間記錄小鼠攝食量、攝水量、體重變化及老化指數評估。行為方面進行活動量試驗，並以單次被動迴避試驗及主動迴避試驗進行學習記憶能力測試。動物犧牲前，進行口服葡萄糖耐受性試驗(OGTT)。犧牲後進行血液生化分析，檢測超氧歧化、觸、麩胱過氧化、麩胱還原、葡萄糖-6-磷酸去氫活性及TBARS、蛋白羰基、總含硫化合物含量。另進行胰臟之胰島素定量，並以組織切片觀察腦部、胰臟β-類澱粉蛋白沉積之情形。結果顯示：實驗各組攝食量、攝水量、體重變化及活動量於四組間均無顯著差異。在老化指數評估方面，3與6月齡雄性及雌性兒茶素組之老化指數總分顯著低於對照組(p＜0.05)。於學習記憶方面，經主動迴避試驗結果發現3及6月齡雄、雌性小鼠實驗組均有較佳的學習記憶能力；另3及6月齡雄、雌性小鼠經單次被動迴避試驗發現實驗組在學習記憶保留上顯著較佳，且達顯著差異(p＜0.05)。而3及6月齡雄、雌性小鼠經OGTT結果發現，實驗組於第0、30、60、90、120分鐘之血糖值皆顯著低於對照組(p<0.05)；在血漿胰島素濃度方面，實驗組於第0、30、60、90、120分鐘之血漿胰島素濃度亦顯著低於對照組 (p<0.05)。在超氧歧化活性部份，三與六月齡雄、雌性小鼠實驗各組間均無顯著差異；而在觸、麩胱過氧化、麩胱還原、葡萄糖-6-磷酸去氫活性及總含硫化合物濃度方面，3與6月齡雄、雌性小鼠之兒茶素組均顯著高於對照組(p<0.05)；兒茶素組之TBARS及蛋白羰基含量則顯著低於對照組(p<0.05)。於腦部、胰臟β-類澱粉蛋白總沉積量及胰島素定量方面，3與6月齡雄、雌性小鼠各組間無顯著差異。綜合以上結果，補充兒茶素可改善老化促進小鼠之學習記憶能力、提升其抗氧化防禦系統並加強其胰島素敏感性。

Catechins were demonstrated to have antioxidant and redusing blood glucose capacity. The purpose of this study was to investigate the effect of catechins on learning and memory ability, antioxidative status, blood glucose and insulin content in senescence accelerated mice. 3- and 6-month-old senescence accelerated male and female mice were divided into four groups: control group, 50, 200 and 800 ppm aqueous solutions of catechins(experimental groups). After 12 weeks of feeding, body weight, food intake, drink amount, aging score, open field activity test, single-trial passive avoidance and active shuttle avoidance test were performed during the experiment. The oral glucose tolerance test (OGTT) was analyzed before sacrificed. The biochemical parameters of serum were analyzed after sacrificed. The activity of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase, glucose-6-phosphate dehydrogenase (G-6-PD), malondialdehyde (MDA) , protein carbonyl and total thiol concentrations and insulin content, pathological examination of brain and pancreas. The results showed that there were no significant differences in the body weight, food intake, drink amount and locomotion among four groups. The aging score of experimental groups were significantly lower than the control group in the 3-and 6-month-old mice (p&lt;0.05). In learning and memory test, experimental groups of 3-and 6-month-old senescence accelerated male and female mice had significantly better in active shuttle avoidance response and single-trial passive avoidance test (p＜0.05). The results of OGTT, experimental groups of 3-and 6-month-old senescence accelerated male and female mice had significantly lower than the control group on blood glucose at 0, 30, 60, 90, 120 minutes (p&lt;0.05). In concentration of plasma insulin, experimental groups had significantly lower than the control group in before and 30, 60, 90, 120 minutes (p&lt;0.05). The SOD activity was no significantly different in both 3-and 6-month old male and female mice. The catalase, GPx, glutathione reductase, G-6-PD activity and total thiol concentration, experimental groups of 3-and 6-month-old senescence accelerated male and female mice had significantly higher than the control group (p＜0.05). The MDA and protein carbonyl concentrations in the experimental groups were significantly lower than the control group. The β-amyloid protein deposition of brain, pancreas and insulin content were no significantly different in the 3-and 6-month male and female mice. From the findings of these results, the supplement of catechins may ameliorate learning and memory ability, antioxidative system and increase insulin sensitivity in SAMP8 mice.

目 錄
頁次
中文摘要 Ⅰ
英文摘要 Ⅲ
目錄 Ⅴ
表目錄 Ⅷ
圖目錄 X

第一章 前言 1

第二章 文獻回顧 5
第一節自由基與活性氧的定義與種類 5
一、自由基與活性氧的定義 5
二、自由基的來源 6
三、自由基與人類疾病之關係 7
四、體內抗氧化防禦系統 10
第二節 老化 11
一、老化之定義 13
二、老化與自由基之相關性 13
三、老化與抗氧化防禦系統 14
四、老化與阿滋海默症

第三節 胰島素 18
一、胰島素於三大營養素中所扮演的角色 18
二、影響胰島素分泌的因子 19

第四節 老化促進小鼠 23
一、老化促進小鼠來源 23
二、老化促進小鼠之老化特徵及抗氧化狀態 23
三、老化促進小鼠之病理特徵 24
四、老化促進小鼠與學習記憶 25
五、老化指數系統

第五節 學習與記憶 30
一、學習記憶的形成 30
二、記憶形成的機制 31
三、學習記憶的實驗方法 32
第六節 兒茶素 35
一、茶之簡介 35
二、茶葉的化學組成 36
三、茶葉的機能性 41
四、兒茶素類的負面影響 51
五、兒茶素類的吸收及分佈 53
第三章 材料與方法 54
第一節 實驗動物 54
第二節 實驗設計 55
第三節 實驗飲水配製 57

第四節 實驗方法與步驟 58
壹、實驗流程 58
貳、活動量測試 60
參、老化指數 60
肆、學習記憶測試 61
伍、葡萄糖耐受性試驗 65
陸、血液生化學分析 65
柒、肝臟抗氧化能力分析 65
捌、血液抗氧化能力分析 77
玖、腦部及胰臟病理切片觀察 79
拾、胰臟胰島素定量 91
第五節 統計分析 93

第四章 結果與討論 94
第一節 體重、攝食量及攝水量 94
第二節 老化指數 97
第三節 活動量 102
第四節 學習與記憶能力 105
第五節 口服葡萄糖耐受性試驗 111
第六節 器官重量 116
第七節 血液生化學分析 116
第八節 肝臟抗氧化能力 122
第九節 血液抗氧化能力 140
第十節 腦部β類澱粉蛋白之沈積 143
第十一節 胰臟β類澱粉蛋白之沈積 150
第十二節 胰臟胰島素定量 154

第五章 結論 157

第六章 參考文獻 159
表目錄
頁次
表一 自由基參與的各種疾病 9
表二 老化指數判定標準 27
表三 SAM之病理生物學表型 29
表四 茶中的多酚類化合物
表五 茶葉成份的機能性分類 47
表六 茶葉中機能性成份的生理效應 48
表七 福壽公司實驗動物飼料組成 56
表八 3月及6月齡雄性SAMP8小鼠餵食
不同濃度兒茶素12週體重及攝食量之變化 95
表九 3月及6月齡雌性SAMP8小鼠餵食
不同濃度兒茶素12週體重及攝食量之變化 96
表十 3月齡雄性SAMP8系小鼠補充兒茶素11週後之
老化指數 98
表十一 3月齡雌性SAMP8系小鼠補充兒茶素11週後之
老化指數 99
表十二 6月齡雄性SAMP8系小鼠補充兒茶素11週後之
老化指數 100
表十三 6月齡雌性SAMP8系小鼠補充兒茶素11週後之
老化指數 101
表十四 3月齡SAMP8系小鼠飲用不同濃度兒茶素11週後
之活動量 103
表十五 6月齡SAMP8系小鼠飲用不同濃度兒茶素11週後
之活動量 104
表十六 三月齡SAMP8系小鼠飲用不同濃度兒茶素12週後
經口服葡萄糖耐受性試驗之結果 112
表十七 六月齡SAMP8系小鼠飲用不同濃度兒茶素12週後
經口服葡萄糖耐受性試驗之結果 114
表十八 3及6月齡雄性SAMP8系小鼠飲用不同濃度兒茶素
12週後之器官重 118
表十九 3及6月齡雌性SAMP8系小鼠飲用不同濃度兒茶素
12週後之器官重 119

表二十 3及6月齡雄性SAMP8系小鼠飲用不同濃度兒茶素
12週後對其血液生化值之影響 120
表二十一 3及6月齡雌性SAMP8系小鼠飲用不同濃度兒茶素
12週後對其血液生化值之影響 121




圖目錄
頁次
圖一 阿滋海默病腦部β-類澱粉蛋白導致氧化壓力及
神經毒性之作用機制 17
圖二 葡萄糖刺激胰島素釋放之機制圖 20
圖三 兒茶素類結構 40
圖四 兒茶素的抗氧化化學結構特性 49
圖五 兒茶素類的抗氧化反應機制 50
圖六 實驗流程圖 59
圖七 活動量裝置圖 63
圖八 主動迴避試驗裝置圖 64
圖九 被動迴避試驗裝置圖 64
圖十 病理組織切片流程圖 87
圖十一 腦部結構圖 88
圖十二 SAMP8小鼠全腦切片圖呈現深褐色β-類澱粉
蛋白沉積 89
圖十三 SAMP8小鼠胰臟切片圖呈現深褐色β-類澱粉蛋白
沉積 90
圖十四 3月齡SAMP8系小鼠飲用不同濃度兒茶素12週後
經主動迴避試驗之逃脫反應次數 106
圖十五 6月齡SAMP8系小鼠飲用不同濃度兒茶素12週後
經主動迴避試驗之逃脫反應次數 107
圖十六 3月齡SAMP8系小鼠飲用不同濃度兒茶素12週後
經單次被動迴避試驗之滯留時間 109
圖十七 6月齡SAMP8系小鼠飲用不同濃度兒茶素12週後經
單次被動迴避試驗之滯留時間 110
圖十八 3月及6月齡雄性SAMP8系小鼠飲用不同濃度
兒茶素12週後之肝臟超氧歧化活性 126
圖十九 3月及6月齡雌性SAMP8系小鼠飲用不同濃度
兒茶素12週後之肝臟超氧歧化活性 127
圖二十 3月及6月齡雄性SAMP8系小鼠飲用不同濃度
兒茶素12週後之肝臟觸活性 128
圖二十一 3月及6月齡雌性SAMP8系小鼠飲用不同濃度
兒茶素12週後之肝臟觸活性 129

圖二十二 3月及6月齡雄性SAMP8系小鼠飲用不同濃度
兒茶素12週後之肝臟麩胱過氧化活性 130
圖二十三 3月及6月齡雌性SAMP8系小鼠飲用不同濃度
兒茶素12週後之肝臟麩胱過氧化活性 131
圖二十四 3月及6月齡雄性SAMP8系小鼠飲用不同濃度
兒茶素12週後之肝臟麩胱還原活性 132
圖二十五 3月及6月齡雌性SAMP8系小鼠飲用不同濃度
兒茶素12週後之肝臟麩胱還原活性 133
圖二十六 3月及6月齡雄性SAMP8系小鼠飲用不同濃度
兒茶素12週後之肝臟丙二醛濃度 134
圖二十七 3月及6月齡雌性SAMP8系小鼠飲用不同濃度
兒茶素12週後之肝臟丙二醛濃度 135
圖二十八 3月及6月齡雄性SAMP8系小鼠飲用不同濃度
兒茶素12週後之肝臟蛋白質羰基濃度 136
圖二十九 3月及6月齡雌性SAMP8系小鼠飲用不同濃度
兒茶素12週後之肝臟蛋白質羰基濃度 137
圖三十 比較3月及6月齡雄性SAMP8系小鼠飲用不同濃度
兒茶素12週後之肝臟總含硫化合物之濃度 138
圖三十一 比較3月及6月齡雌性SAMP8系小鼠飲用不同濃度
兒茶素12週後之肝臟總含硫化合物之濃度 139
圖三十二 比較3月及6月齡雄性SAMP8系小鼠飲用不同濃度
兒茶素12週後之血液葡萄糖-6-磷酸去氫之活性 141
圖三十三 比較3月及6月齡雌性SAMP8系小鼠飲用不同濃度
兒茶素12週後之血液葡萄糖-6-磷酸去氫之活性 142
圖三十四 比較不同濃度之兒茶素對3月齡雄性SAMP8小鼠
腦中β-類澱粉蛋白沉積平均面積百分比 145
圖三十五 比較不同濃度之兒茶素對3月齡雌性SAMP8小鼠
腦中β-類澱粉蛋白沉積平均面積百分比 146
圖三十六 比較不同濃度之兒茶素對6月齡雄性SAMP8小鼠
腦中β-類澱粉蛋白沉積平均面積百分比 147
圖三十七 比較不同濃度之兒茶素對6月齡雌性SAMP8小鼠
腦中β-類澱粉蛋白沉積平均面積百分比 148

圖三十八 SAMP8小鼠腦中β-類澱粉蛋白沉積呈陽性反應 149
圖三十九 SAMP8小鼠腦中β-類澱粉蛋白沉積呈陰性反應 149
圖四十 比較不同濃度之兒茶素對3月及6月齡雄性SAMP8
小鼠胰臟β-類澱粉蛋白沉積平均面積百分比 151
圖四十一 比較不同濃度之兒茶素對3月及6月齡雌性SAMP8
小鼠胰臟β-類澱粉蛋白沉積平均面積百分比 152
圖四十二 SAMP8小鼠胰臟β-類澱粉蛋白沉積呈陽性反應 153
圖四十三 SAMP8小鼠胰臟β-類澱粉蛋白沉積呈陰性反應 153
圖四十四 比較不同濃度之兒茶素對3月及6月齡雄性SAMP8
小鼠胰臟胰島素含量 155
圖四十五 比較不同濃度之兒茶素對3月及6月齡雌性SAMP8
小鼠胰臟胰島素含量 156

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