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標題: | 維生素E對餵食新鮮油或炸油之自體免疫鼠病情的影響 The effects of vitamin E on the progress of autoimmune disease in autoimmune–prone mice fed fresh oil or frying oil diet |
作者: | Chia-Chien Hsieh 謝佳倩 |
指導教授: | 林璧鳳(Bi-Fong Lin) |
關鍵字: | 全身性紅斑狼瘡,維生素E,介白質-2,炸油, SLE, Frying oil,alpha-tocopherol,IL-2, |
出版年 : | 2005 |
學位: | 博士 |
摘要: | 本研究係探討維生素E的補充對自體免疫鼠病情的影響,分別對攝食炸油(10%炸油+5%新鮮大豆油)或一般低油(5%新鮮大豆油)的自體免疫鼠MRL/lpr或NZB/W F1鼠,添加5倍或10倍的維生素E (all-rac-alpha-tocopheryl acetate, alpha-TOC),追蹤小鼠自體抗體生成、尿蛋白和生命期之變化。並探討是否經由影響氧化壓力、免疫細胞族群、脂肪酸組成,進而影響發炎反應等機轉,以了解維生素E對自體免疫疾病的利弊。實驗飼料包括:炸油 (SF)、炸油補充10倍維生素E (SFE10, SF + 550mg/kg)、低油 (E1)、低油補充10倍維生素E (E10, 5%新鮮油+ alpha-TOC 500mg/kg) 或缺乏維生素E (E0)。結果顯示,炸油添加10倍維生素E對MRL/lpr與NZB/W F1自體免疫小鼠,有益於延緩小鼠病情惡化,在NZB/W F1鼠延長生命期達顯著差異。缺乏維生素E與炸油飲食,皆會造成紅血球溶血增加與組織TBARS上升,炸油補充維生素E,可顯著增加組織中維生素E含量,降低組織TBARS與紅血球溶血率,抗雙股DNA抗體生成較低,但新鮮油添加維生素E則無顯著變化。雖然缺乏維生素E增加組織氧化壓力,但抑制B細胞增生反應,降低自體抗體生成。在脂肪酸組成方面,SFE10飲食會抑制脾臟細胞脂肪酸LA衍生成AA,可能降低促發炎介質PGE2衍生,但本實驗結果未達顯著性。對免疫細胞的影響,E0與SF飲食,增加T細胞比例,促進IL-2分泌。SFE10組、E10組或ED組均顯著抑制IFN-gamma與IL-6的分泌,減少MHC II的表現,可能為降低自體抗體生成的原因。E10會降低NZB/W F1鼠脾臟細胞自發性IL-2的分泌,與前報導MRL/lpr鼠動物及細胞實驗,高劑量維生素E顯著抑制鼠脾臟細胞IL-2的分泌結果一致。
因此,由體外添加維生素E細胞培養,探討高劑量抑制IL-2分泌的影響機制,是否透過增加Th1的細胞凋亡或抑制IL-2的訊息傳遞。故利用OVA-specific Tg轉殖小鼠分離培養已分化的Th1與Th2細胞,探討 The purpose of this study was to investigate the effect of vitamin E supplementation on the autoimmune disease in NZB/W F1 female mice. The animal model and cell culture experiments were conducted to extend the mechanism of vitamin E supplementation in different dietary condition. The mice were fed an AIN-76 diet containing either 10 % oxidized frying oil+5 % fresh oil (SF), SF supplemented with all-rac-alpha-tocopheryl acetate at a level of 550 mg/kg diet (SFE10), 5 % fresh oil (E1), E1 supplemented with all-rac-alpha-tocopheryl acetate at 500 mg/kg (E10) or vitamin E deficiency (E0) respectively. The results showed that both MRL/lpr and NZB/W F1 mice fed the SFE10 diet convalesced growth and food intake. NZB/W F1 mice fed the SFE10 diet had lower anti-dsDNA IgG antibody level and longer life span than those fed the SF diets. The vitamin E supplementation in the oxidized oil significantly decreased TBARS values in the kidney and spleen of NZB/W F1 mice. The RBC hemolysis and TBARS values were increase in mice fed the ED diet. IFN-gamma and IL-6 production by mitogen-stimulated splenocytes decreased in mice fed on the SFE10, E10 and E0 diets. The IL-2 secretion by PHA-stimulation significantly increased in the SFE10 and E0 groups. The splenocytes from mice fed on the E0 diet have lower proliferative responses by PHA and LPS stimulation. The percentage of T cells significantly increased while major histocompatibility complex (MHC) class II-bearing cells decresed in the spleens of the SFE10 and E0 groups. The SFE10 group had significantly higher LA composition and tended to have lower AA and urinary bicycle-PGE2 than those of the SF diet group. We previously demonstrated that high dose of alpha-tocopherol succinate inhibited IL-2 mRNA expression and production in PHA-activated splenocytes of MRL/lpr mice. The na |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/39261 |
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