NF-κB和Nrf2在DHA拮抗1-溴丙烷中枢神经毒性中的作用

发布时间：2018-01-02 10:03

  本文关键词：NF-κB和Nrf2在DHA拮抗1-溴丙烷中枢神经毒性中的作用　出处：《山东大学学报(医学版)》2016年04期 　论文类型：期刊论文

  更多相关文章： -溴丙烷 中枢神经毒性 核因子-κB NF-E相关因子 二十二碳六烯酸

【摘要】：目的观察核因子-κB(NF-κB)与NF-E2相关因子2(Nrf2)在DHA拮抗1-溴丙烷(1-BP)中枢神经毒性中的作用。方法 48只Wistar大鼠随机分为对照组、1-BP组、250 mg/kg DHA+1-BP组(LDHA组)和500 mg/kgDHA+1-BP组(HDHA组)。各组动物均经口给予1-BP和DHA,连续12 d。Western blotting和免疫荧光检测大脑前额叶皮层胞浆组分中NF-κB、Nrf2的激活、下游Ⅱ相酶的蛋白表达、大脑星形胶质细胞的激活及4-HNE氧化修饰蛋白质的变化。结果与对照组比较,1-BP组大脑胞浆和胞核中NF-κB、Nrf2的表达以及下游Ⅱ相酶的蛋白表达升高(P0.05),与1-BP组相比,LDHA组和HDHA组NF-κB及Ⅱ相酶的蛋白表达降低(P0.05),而Nrf2表达增加(P0.05);与对照组比较,1-BP组星形胶质细胞激活数目增加,与1-BP组相比,LDHA组和HDHA组细胞激活数目减少;1-BP组4-HNE修饰蛋白含量与对照组相比显著增加(P0.05),与1-BP组比较,LDHA组和HDHA组4-HNE蛋白含量降低(P0.05)。结论 DHA通过抑制NF-κB并且激活Nrf2,呈现对1-BP中枢神经毒性的拮抗作用。
[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.

【作者单位】： 山东大学公共卫生学院毒理学系;
【基金】：国家自然科学基金(81172708) 山东省科技攻关计划课题(2011GSF11814)
【分类号】：R114
【正文快照】： 1-溴丙烷(1-bromopropane,1-BP)作为一种有机溶剂应用广泛。研究表明,1-BP的毒性与氧化应激有密切关系。1-BP暴露能导致大鼠大脑谷胱甘肽(glutathione,GSH)耗竭,降低谷胱甘肽还原酶(glutathione reductase,GR)、γ-谷氨酰胺半胱氨酸连接酶((glutamate cysteine ligase,γ-GCL)，

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