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山东大学学报(医学版) ›› 2016, Vol. 54 ›› Issue (4): 84-88.doi: 10.6040/j.issn.1671-7554.0.2015.791

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NF-κB和Nrf2在DHA拮抗1-溴丙烷中枢神经毒性中的作用

王增金,袁华,杨俊林,谢克勤,赵秀兰   

  1. 山东大学公共卫生学院毒理学系, 山东 济南 250012
  • 收稿日期:2015-08-20 出版日期:2016-04-10 发布日期:2016-04-10
  • 通讯作者: 赵秀兰. E-mail: zhao.xl@sdu.edu.cn E-mail:zhao.xl@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(81172708);山东省科技攻关计划课题(2011GSF11814)

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

WANG Zengjin, YUAN Hua, YANG Junlin, XIE Keqin, ZHAO Xiulan   

  1. Department of Toxicology, School of Public Health, Shandong University, Jinan 250012, Shandong, China
  • Received:2015-08-20 Online:2016-04-10 Published:2016-04-10

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。

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

Abstract: 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 were randomly divided into control group, 1-BP group, 250 mg/kg DHA+1-BP group(LDHA group)and 500 mg/kg DHA+1-BP group(HDHA group). 1-BP and DHA were 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 were measured with Western blotting and immunofluorescence. Results The cortex cytoplasmic and nuclear protein expressions of NF-κB, Nrf2 and phase II enzyme protein were significantly higher in the control group than in 1-BP group(P<0.05). Compared with the 1-BP group, the expression of NF-κB and II enzyme protein were significantly lower (P<0.05)but the level of Nrf2 was significantly higher in LDHA group and HDHA group(P<0.05). Compared with the control group, activated astrocytes in 1-BP group were significantly increased, while those in LDHA group and HDHA group were significantly decreased. The content of 4-HNE modified protein in 1-BP group was significantly higher than in the control group(P<0.05). Compared with the 1-BP group, the content of 4-HNE modified protein was significantly lower 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. 山 东 大 学 学 报 (医 学 版)54卷4期 -王增金,等.NF-κB和Nrf2在DHA拮抗1-溴丙烷中枢神经毒性中的作用 \=-

Key words: 1-bromopropane, Nuclear factor-kappa B, NF-E2-related factor 2, Docosahexaenoic acid, Central nervous system toxicity

中图分类号: 

  • R994.6
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