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研究生:吳郁嫻
研究生(外文):Yu-Hsien Wu
論文名稱:多元不飽和脂肪酸對巨噬細胞及脂蛋白元E剔除小鼠氧化還原狀態及脂質運輸之影響
論文名稱(外文):The effects of polyunsaturated fatty acids on the redox status and lipid trafficking in macrophages 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:2004
畢業學年度:92
語文別:中文
中文關鍵詞:多元不飽和脂肪酸脂蛋白元E剔除小鼠
外文關鍵詞:polyunsaturated fatty acidsapoE knockout mice
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許多過去之研究均指出魚油及其中之n-3多元不飽和脂肪酸 (n-3 PUFAs) 具有預防心血管疾病的功效,然而到底是透過什麼機制能達成這樣的保護功效則仍不清楚。本研究,我們分別探討不同的PUFAs對於脂蛋白元E剔除小鼠與巨噬細胞之氧化還原狀態與脂質運輸的影響。
  在動物實驗中,將四十隻脂蛋白元E剔除小鼠分成五組,每組餵予對照組、二十碳五烯酸 (EPA)、二十二碳六烯酸 (DHA)、花生四烯酸 (AA) 和亞麻油酸 (LA)。強制餵食十週後將小鼠犧牲,取其血漿、肝臟和主動脈等樣本做分析。餵食AA、EPA以及DHA的脂蛋白元E剔除小鼠,其血漿中的總膽固醇、高密度脂蛋白膽固醇與低密度脂蛋白膽固醇都沒有顯著的差異。然而,餵食LA的小鼠,其血漿及肝臟中的三酸甘油酯都有顯著的上升。餵食AA及DHA之脂蛋白元E剔除小鼠肝臟中的銅鋅超氧化物歧化酶 (Cu,Zn-SOD) 活性顯著上升,但是並不會增加麩胱胺酸過氧化物酶及過氧化氫酶的活性。在主動脈動脈粥狀硬化病灶處的觀察,可以看到餵食DHA的小鼠有最少的斑塊堆積,而餵食LA的小鼠斑塊堆積的情況最嚴重。在細胞模式中,針對J774A.1巨噬細胞,添加AA、EPA、DHA及LA會降低膽固醇的送出,必須同時存在9-cis A酸 (9-cis retinoic acid) 的情況下才能增加膽固醇的送出。至於在人類巨噬細胞方面,不管在有無9-cis retinoic acid存在的情況下,添加不同的PUFAs對於膽固醇的送出與送入都沒有顯著的差別。
  研究之數據顯示,DHA為魚油中最具有防止動脈粥狀硬化發生的有效成份。在脂蛋白元E剔除小鼠中,DHA改善動脈粥狀硬化病灶的形成,可能是透過增加SOD活性,而不是藉由降低脂質達成。然而我們並不能排除否有其他的抗動脈粥狀硬化形成的機制涉入,而仍須更進一步研究探討。
Many previous studies indicated that fish oils and marine n-3 polyunsaturated fatty acids (PUFAs) have benefits with regard to the prevention of cardiovascular diseases. However, the mechanism contributing to the benefit of n-3 PUFAs has not been fully understood. In present study, we investigated the effect of different PUFAs on the redox status and lipid trafficking in apoE knockout mice and macrophages, respectively.
In animal experiment, forty apoE knockout mice were divided into five groups including the control, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and linoleic acid (LA) groups. After being fed by gavage for ten weeks, animals were sacrificed and specimens of blood, liver, and aorta were collected, respectively. There was no significant difference in plasma levels of total cholesterol, HDL-C, and LDL-C among groups of apoE knockout mice fed with AA, EPA, and DHA. However, plasma and liver levels of triglyceride were significantly increased in mice fed with LA. The levels of hepatic cuprozinc-superoxide dismutase (Cu,Zn-SOD) were significantly higher in mice fed with AA and DHA, but the levels of hepatic glutathione peroxidase and catalase activities did not show difference among groups. The mice treated with DHA had the least content of atherosclerotic lesions in the aorta, while the mice treated with LA had the most. In cellular study, treatment of AA, EPA, DHA, and LA decreased the cholesterol efflux in J774A.1 macrophages, but treatment of both PUFAs and 9-cis retinoic acid increased cholesterol efflux. There was no significant difference in cholesterol efflux and influx among groups of human primary macrophages treated with different PUFAs in the presence or absence of 9-cis retinoic acid.
Data from this study suggest that DHA may be the most active constituent of fish oils to prevent the process of atherosclerosis. DHA reduced the formation of atherosclerotic lesions in the aorta of apoE knockout mice probably via increasing SOD activity, not via lipid-lowering effect. However, we cannot rule out the involvement of other antiatherogenic mechanisms at present.
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