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本帖產(chǎn)生 1 個翻譯EPI ，點擊這里進行查看

xiaowanzi9

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[求助] 求助翻譯兩段話，量大

Besides well-described actions on the immune system (see earlier),
application of dimethyl fumarate led to effects on endogenous
cellular antioxidative pathways involving the transcription
factor nuclear (erythroid-derived 2) related factor (Nrf2) [26••].
Nrf2 is a redox-sensitive leucine zipper transcription factor,
which contains a domain for interaction with the cytoplasmatic
protein kelch-like ECH-associated protein (Keap-1) [27]. In
vitro, application of dimethyl fumarate resulted in stabilization
of Nrf2, activation of Nrf2-dependent transcriptional activity, and
expression of NADPH:quinolone oxidoreductase 1 (NQO1) as a
prototypic target gene [28]. Furthermore, application of dimethyl
fumarate or MMF involved direct modification of Keap-1 [26••].
On a cellular level, the application of MMF enhanced neuronal
survival and protected glial cells against oxidative stress. This
action of dimethyl fumarate on cellular resistance to oxidative
damage in primary cultures of CNS cells was further substantiated
in independent studies [29, 30•] where protective effects
were abolished in cells with Nrf2 deficiency [30•]. In vivo,
increased levels of Nrf2 were detected in the CNS of dimethyl
fumarate treated mice with myelin oligodendrocyte glycoprotein
induced EAE. In the very late stage of myelin oligodendrocyte
glycoprotein induced EAE, dimethyl fumarate ameliorated the
disease course and improved preservation of myelin, axons, and
neurons. This effect was not seen in Nrf2-deficient mice [26••].

In summary, activation of Nrf2-dependent antioxidative pathways
seems to be an important mechanism of action of dimethyl
fumarate. Since oxidative stress may play a major role in the
pathogenesis of axonal damage and tissue injury inMS [31], the
dimethyl fumarate mediated pharmacological modulation of
Nrf2-mediated signaling is an interesting and new therapeutic
target not only in experimental models, but also in humans.

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genhunter

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xiaowanzi9: 金幣+50, 翻譯EPI+1, ★★★★★最佳答案, 謝謝你 2015-05-25 10:38:37

除了已經(jīng)很好描述了的對免疫系統(tǒng)的效果之外（見前面），反丁烯二酸二甲酯還可通過細胞核轉(zhuǎn)錄
因子(紅細胞來源的）相關(guān)因子（Nrf2）影響內(nèi)源性的抗氧化通路。Nrf2是一種對氧化還原敏感的亮氨酸拉鏈轉(zhuǎn)錄因子，它含一個能與細胞質(zhì)蛋白Kelch-like ECH-associated protein（keap-1）相互作用域[ 27 ]。在
體外實驗中，使用反丁烯二酸二甲酯導(dǎo)致Nrf2變得穩(wěn)定，從而激活Nrf2依賴的轉(zhuǎn)錄活性，并表達它的一個
典型的靶基因NADPH：喹諾酮類藥物的氧化還原酶1（NQO1）[ 28 ]。此外，應(yīng)用反丁烯二酸二甲酯或MMF (估計是反丁烯二酸單甲酯)還參與keap-1 的直接修飾。在細胞水平上，使用MMF可以增強神經(jīng)細胞的存活和保護神經(jīng)膠質(zhì)細胞受氧化應(yīng)激(的損傷)。這種反丁烯二酸二甲酯對原代培養(yǎng)的中樞神經(jīng)細胞抵抗氧化作用引起的損傷已有獨立的研究進一步證實[ 29，30 ]，并且保護作用在沒有Nrf2表達的細胞中不存在•[ 30 ]。在體內(nèi)，在髓鞘少突膠質(zhì)細胞糖蛋白誘導(dǎo)的EAE模型的小鼠中反丁烯二酸二甲酯處理增加Nrf2的表達。在髓鞘少突膠質(zhì)細胞糖蛋白誘導(dǎo)的EAE的晚期，反丁烯二酸二甲酯減緩了病程發(fā)展及改善了對髓鞘，軸突及神經(jīng)細胞存活。在Nrf2的基因敲除小鼠內(nèi)沒有這種效果。
總之，Nrf2依賴抗氧化通路的激活似乎是一個反丁烯二酸二甲酯作用的重要機制作用。由于氧化應(yīng)激可能在軸突損傷和 (MS: multiple sclerosis) 多發(fā)性硬化癥組織損傷中起主要作用[ 31 ]，由富馬酸二甲酯介導(dǎo)的藥理調(diào)控Nrf2介導(dǎo)的信號轉(zhuǎn)遞是一個有趣的和新的治療靶點不僅在實驗動物模型中，而且在人類(治療中也有意義)。

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2樓2015-05-21 16:08:51