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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-κB (NF-κB) and NF-E2-related factor 2 (Nrf2) in antagonizing central neurotoxicity of 1-bromopropane (1-BP) Methods 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). Animals in each group were given 1-BP and DHA orally for 12 consecutive days. Western blotting and immunofluorescence were used to detect the activation of NF-κB and Nrf2 in the prefrontal cortex and the expression of the downstream phase Ⅱ enzyme, the activation of the astrocytes and the changes of 4-HNE oxidatively-modified proteins. Results Compared with the control group, the expression of NF-κB and Nrf2 in the cytoplasm and nucleus of the 1-BP group and the expression of the downstream phase II enzyme increased (P <0.05). Compared with the 1-BP group, the LDHA group (P <0.05), while the expression of Nrf2 increased (P <0.05). Compared with the control group, the number of astrocytes in 1-BP group increased and the expression of NF- Compared with 1-BP group, the number of cell activation in LDHA group and HDHA group decreased; the content of 4-HNE modified protein in 1-BP group increased significantly compared with control group (P <0.05) Group 4-HNE protein content decreased (P <0.05). Conclusion DHA can inhibit 1-BP central neurotoxicity by inhibiting NF-κB and activating Nrf2.