NF-κB和Nrf2在DHA拮抗1-溴丙烷中枢神经毒性中的作用  

DHA attenuated central neurotoxicity of 1-bromopropane by activating NF-κB and Nrf2

作　　者：王增金[1] 袁华[1] 杨俊林[1] 谢克勤[1] 赵秀兰[1] 

机构地区：[1]山东大学公共卫生学院毒理学系,山东济南250012

出　　处：《山东大学学报（医学版）》2016年第4期84-88,93,共6页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81172708);山东省科技攻关计划课题(2011GSF11814)

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(P<0.05),与1-BP组相比,LDHA组和HDHA组NF-κB及Ⅱ相酶的蛋白表达降低(P<0.05),而Nrf2表达增加(P<0.05);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(P<0.05),与1-BP组比较,LDHA组和HDHA组4-HNE蛋白含量降低(P<0.05)。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。Objective To observe the role of nuclear factor-kappa B（ NF-κB） and NF-E2-related factor 2（ Nrf2） in DHA antagonizing central nervous system（ CNS） neurotoxicity of 1-bromopropane（ 1-BP）. Methods A total of 48 Wistar rats w ere randomly divided into control group,1-BP group,250 mg / kg DHA ＋ 1-BP group（ LDHA group） and500 mg / kg DHA ＋ 1-BP group（ HDHA group）. 1-BP and DHA w ere orally administered to all animals for 12 consecutive days. The prefrontal cortex cytoplasmic protein activation of NF-κB,Nrf2,phase II enzyme protein,activation of astrocyte and 4-hydroxy-2-nonenal（ 4-HNE） modified protein w ere measured w ith Western blotting and immunofluorescence. Results The cortex cytoplasmic and nuclear protein expressions of NF-κB,Nrf2 and phase II enzyme protein w ere significantly higher in the control group than in 1-BP group（ P〈0. 05）. Compared w ith the 1-BP group,the expression of NF-κB and II enzyme protein w ere significantly low er（ P〈0. 05） but the level of Nrf2 w as significantly higher in LDHA group and HDHA group（ P〈0. 05）. Compared w ith the control group,activated astrocytes in 1-BP group w ere significantly increased,w hile those in LDHA group and HDHA group w ere significantly decreased. The content of 4-HNE modified protein in 1-BP group w as significantly higher than in the control group（ P〈0. 05）. Compared w ith the 1-BP group,the content of 4-HNE modified protein w as significantly low er in LDHA group and HDHA group（ P〈0. 05）. Conclusion DHA may show antagonism against CNS toxicity of 1-BP by inhibiting NF-κB and activating Nrf2.

关 键 词：1-溴丙烷 中枢神经毒性 核因子-ΚB NF-E2相关因子 二十二碳六烯酸 

分 类 号：R994.6[医药卫生—毒理学]