NF-κB和Nrf2在DHA拮抗1-溴丙烷中樞神經(jīng)毒性中的作用
發(fā)布時(shí)間:2018-01-02 10:03
本文關(guān)鍵詞:NF-κB和Nrf2在DHA拮抗1-溴丙烷中樞神經(jīng)毒性中的作用 出處:《山東大學(xué)學(xué)報(bào)(醫(yī)學(xué)版)》2016年04期 論文類(lèi)型:期刊論文
更多相關(guān)文章: -溴丙烷 中樞神經(jīng)毒性 核因子-κB NF-E相關(guān)因子 二十二碳六烯酸
【摘要】:目的觀(guān)察核因子-κB(NF-κB)與NF-E2相關(guān)因子2(Nrf2)在DHA拮抗1-溴丙烷(1-BP)中樞神經(jīng)毒性中的作用。方法 48只Wistar大鼠隨機(jī)分為對(duì)照組、1-BP組、250 mg/kg DHA+1-BP組(LDHA組)和500 mg/kgDHA+1-BP組(HDHA組)。各組動(dòng)物均經(jīng)口給予1-BP和DHA,連續(xù)12 d。Western blotting和免疫熒光檢測(cè)大腦前額葉皮層胞漿組分中NF-κB、Nrf2的激活、下游Ⅱ相酶的蛋白表達(dá)、大腦星形膠質(zhì)細(xì)胞的激活及4-HNE氧化修飾蛋白質(zhì)的變化。結(jié)果與對(duì)照組比較,1-BP組大腦胞漿和胞核中NF-κB、Nrf2的表達(dá)以及下游Ⅱ相酶的蛋白表達(dá)升高(P0.05),與1-BP組相比,LDHA組和HDHA組NF-κB及Ⅱ相酶的蛋白表達(dá)降低(P0.05),而Nrf2表達(dá)增加(P0.05);與對(duì)照組比較,1-BP組星形膠質(zhì)細(xì)胞激活數(shù)目增加,與1-BP組相比,LDHA組和HDHA組細(xì)胞激活數(shù)目減少;1-BP組4-HNE修飾蛋白含量與對(duì)照組相比顯著增加(P0.05),與1-BP組比較,LDHA組和HDHA組4-HNE蛋白含量降低(P0.05)。結(jié)論 DHA通過(guò)抑制NF-κB并且激活Nrf2,呈現(xiàn)對(duì)1-BP中樞神經(jīng)毒性的拮抗作用。
[Abstract]:Objective To observe the effect of nuclear factor kappa B (NF- K B) and NF-E2 related factor 2 (Nrf2) in the DHA antagonist 1- bromopropane (1-BP) induced neurotoxicity in rats. Methods 48 male Wistar rats were randomly divided into control group, 1-BP group, mg/kg 250 DHA+1-BP group (group LDHA) and group mg/kgDHA+1-BP (500 HDHA group). Each animal was treated with 1-BP and DHA, 12 consecutive d.Western blotting and immunofluorescence assay in cortex cytosolic fractions of NF- kappa B, Nrf2 activation, expression of downstream phase II enzyme protein, brain astrocyte activation and oxidative modification of 4-HNE protein changes. Results compared with the control group group 1-BP, brain cytoplasm and nucleus of NF- kappa B, the expression of Nrf2 and the downstream phase II enzyme protein level (P0.05), compared with the 1-BP group, the expression of LDHA group and HDHA group NF- kappa B and phase II enzyme protein (P0.05), and reduce the expression of Nrf2 increased (P0.05); and compared to the control group, 1-BP group star The activation of glial cells increase in number, compared with the 1-BP group, LDHA group and HDHA group decreased the number of 1-BP cell activation; group 4-HNE modified protein content increased significantly compared with the control group (P0.05), compared with 1-BP group, LDHA group and HDHA group decreased 4-HNE protein content (P0.05). Conclusion DHA through inhibition of NF kappa B and NF- the activation of Nrf2 showed inhibition on 1-BP induced neurotoxicity.
【作者單位】: 山東大學(xué)公共衛(wèi)生學(xué)院毒理學(xué)系;
【基金】:國(guó)家自然科學(xué)基金(81172708) 山東省科技攻關(guān)計(jì)劃課題(2011GSF11814)
【分類(lèi)號(hào)】:R114
【正文快照】: 1-溴丙烷(1-bromopropane,1-BP)作為一種有機(jī)溶劑應(yīng)用廣泛。研究表明,1-BP的毒性與氧化應(yīng)激有密切關(guān)系。1-BP暴露能導(dǎo)致大鼠大腦谷胱甘肽(glutathione,GSH)耗竭,降低谷胱甘肽還原酶(glutathione reductase,GR)、γ-谷氨酰胺半胱氨酸連接酶((glutamate cysteine ligase,γ-GCL),
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