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研究生:黃潤元
研究生(外文):Jun-Yuan Huang
論文名稱:多元不飽和脂肪酸對大腦星狀神經膠細胞及脂蛋白元E剔除小鼠氧化還原狀態之影響
論文名稱(外文):Effects of polyunsaturated fatty acids on the redox status in brain astrocytes and apoE knockout mice.
指導教授:姜安娜姜安娜引用關係
指導教授(外文):An-Na Chiang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生物化學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2003
畢業學年度:91
語文別:中文
論文頁數:95
中文關鍵詞:多元不飽和脂肪酸星狀神經膠細胞脂蛋白元E剔除小鼠抗氧化酵素
外文關鍵詞:polyunsaturated fatty acidsastrocyteapoE knockout miceantioxidant enzyme
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摘要
大腦中的脂質含有相當高比例的多元不飽和脂肪酸,這些多元不飽和脂肪酸被認為與認知等腦功能有關,然而多元不飽和脂肪酸也是自由基容易攻擊的目標而會產生脂質過氧化物。本研究的主題是利用大腦皮層星狀神經膠細胞為模式,探討補充多元不飽和脂肪酸是否會影響腦細胞的氧化還原狀態。實驗結果顯示,以花生油四烯酸 (arachidonic acid,AA) 及二十二碳六烯酸 (docosahexaenoic acid,DHA) 處理能增加細胞中超氧陰離子 (O2·-) 的含量。當DHA及二十碳五烯酸 (eicosapentaenoic acid,EPA) 處理時,細胞內過氧化氫 (H2O2) 則減少。以四種多元不飽和脂肪酸處理,則都能使過氧化氫酶 (catalase) 的活性增強。由上述結果可發現,大腦皮層星狀神經膠細胞在面對多元不飽和脂肪酸處理時,會採取一種適應機制,活化了細胞內抗氧化酵素來清除過多的自由基產生。此外,加入了蛋白質激酶C (protein kinase C,PKC) 的抑制劑GF109203X之後,能夠減緩細胞內自由基的產生,所以可知PKC與多元不飽和脂肪酸所引起的自由基產生有關。
本論文亦採用脂蛋白元E剔除小鼠 (apoE knockout mice) 為動物模式,探討多元不飽和脂肪酸對生物體所造成氧化還原狀態之影響。結果顯示,補充DHA能使小鼠肝臟中超氧化物歧化酶 (superoxide dismutase,SOD) 活性增強,且能增加血漿中高密度脂蛋白 (high density lipoprotein,HDL) 和減少低密度脂蛋白 (low density lipoprotein,LDL),顯示DHA可能為魚油具有抗動脈粥狀硬化的重要成分之一。

Abstract
Lipids of brain tissue and brain cells contain high proportions of long-chain polyunsaturated fatty acids (PUFAs). Composition of PUFAs was considered to couple the cognitive functions in brain. However, PUFAs may also be the target for lipid oxidation or free radical generation. The objective of this study was to address whether supplementation with long-chain PUFAs would change redox status in brain cells. At the beginning, we conducted a study to investigate the biological effect of PUFAs on redox status in cortical astrocytes. The results showed that treatment of cortical astrocytes with arachidonic acid (AA) and docosahexaenoic acid (DHA) increased the production of superoxide (O2·-). The production of hydrogen peroxide (H2O2) was decreased with treatment of DHA and eicosapentaenoic acid (EPA). The activity of catalase was increased with treatment of all PUFAs. These data indicate that cortical astrocytes appear to respond to PUFAs treatment by an adaptive mechanism, namely the induction of antioxidant enzymes to remove the overproduction of free radicals. Moreover, addition of a protein kinase C (PKC) inhibitor, GF109203X, attenuated free radicals production induced by PUFAs. Thus, PKC is involved in the PUFA-induced free radicals production pathway.
We also used apoE knockout mice as an animal model to assess the role of PUFAs in the response of oxidative stress in vivo. Dietary supplementation with DHA was associated with an induction of SOD activity in mouse liver. DHA supplementation increased plasma levels of HDL-cholesterol but decreased levels of LDL-cholesterol. These results suggest that DHA seems to be the active component of fish oil that could be beneficial for the prevention of atherosclerosis.

目錄
內 容 頁 數
中文摘要…………………………………………………………….I
英文摘要……………………………………………………………III
緒 論…………………………………………………………….1
實驗材料…………………………………………………………….9
實驗方法…………………………………………………………...13
實驗結果…………………………………………………………...41
討 論…………………………………………………………...51
圖 表…………………………………………………………...60
參考文獻…………………………………………………………...84

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10. 不飽和脂肪酸調控小鼠C2C12肌纖維細胞粒線體生合成之探討
11. 在apoE基因剔除小鼠動脈粥狀硬化發展過程中主動脈之肌凝蛋白去磷酸酶表現量的變化
12. 長期慢性運動對ApoE基因剔除小鼠胸主動脈血管之細胞凋亡相關蛋白表現的影響
13. 補充n-3不飽和脂肪酸對阿茲海默症病患其延緩智能退化之效果評估
14. RNA解螺旋酶CAP-Rf與p68之間交互作用之探討
15. CREB蛋白因生長休止基因七磷酸化而活化:生長休止基因七蛋白透過蛋白質激化酵素A磷酸化而移位並誘發CREB蛋白磷酸化及神經軸突發展
 
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