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目的观察甲基汞对大鼠脑皮质Nrf2、HO-1、γ-GCS、GPx-1 mRNA和蛋白表达的影响,探讨MK-801对其是否具有拮抗作用。方法 Wistar大鼠随机分成4组,对照组:皮下及腹腔注射生理盐水;低、高剂量甲基汞染毒组:皮下注射生理盐水,2 h后分别腹腔注射4和12μmol/kg的氯化甲基汞,MK-801预处理组:皮下注射0.3μmol/kg的MK-801,2 h后腹腔注射12μmol/kg的氯化甲基汞;注射容量为5 ml/kg,干预隔日1次,染毒每日1次,连续干预与染毒4周。最后一次染毒24 h后,处死大鼠取大脑皮质,测定大脑皮质汞含量及Nrf2、HO-1、γ-GCS、GPx-1 mRNA及蛋白表达水平。结果随着染汞剂量的增加,脑内汞含量明显升高;脑皮质内Nrf2、HO-1、γ-GCS的mRNA及蛋白表达均明显升高,GPx-1的mRNA及蛋白表达明显降低。MK-801预处理组较高剂量甲基汞染毒组Nrf2、HO-1的mRNA及蛋白表达明显降低,GPx-1的mRNA及蛋白表达明显升高,对γ-GCS的mRNA及蛋白表达未见明显改变。结论甲基汞可导致大鼠脑皮质Nrf2、HO-1、γ-GCS的mRNA及蛋白表达上调和GPx-1的mRNA及蛋白表达下调,MK-801对甲基汞致大鼠脑皮质Nrf2、HO-1、γ-GCS、GPx-1表达的变化有一定的拮抗作用。
Objective To observe the effect of methylmercury on the expression of Nrf2, HO-1, γ-GCS and GPx-1 mRNA and protein in the rat cerebral cortex and to explore whether MK-801 has an antagonistic effect on it. Methods Wistar rats were randomly divided into 4 groups, control group: subcutaneous and intraperitoneal injection of normal saline; low and high doses of methylmercury exposure group: subcutaneous injection of saline, 2 h after intraperitoneal injection of 4 and 12μmol / kg of chloride Base Mercury, MK-801 pretreatment group: MK-801 0.3μmol / kg subcutaneously was injected intraperitoneally with 12μmol / kg methylmercury chloride for 2 h; injection volume was 5 ml / kg, 1 drug daily, continuous intervention and exposure for 4 weeks. After the last exposure, the rats were sacrificed and the cerebral cortex was sacrificed. The content of mercury and the expression of Nrf2, HO-1, γ-GCS and GPx-1 mRNA and protein in cerebral cortex were determined. Results The content of mercury in the brain increased significantly with the increase of the dose of mercury in the brain. The mRNA and protein expressions of Nrf2, HO-1 and γ-GCS in the cerebral cortex were significantly increased, while the mRNA and protein expression of GPx-1 in the brain decreased significantly. The mRNA and protein expressions of Nrf2 and HO-1 in MK-801 pretreatment group were significantly lower than those in methylmercury exposure group, and the mRNA and protein expressions of GPx-1 were significantly increased. The mRNA and protein expression of γ-GCS See obvious change. Conclusion Methylmercury can up-regulate the mRNA and protein expression of Nrf2, HO-1 and γ-GCS in rat cerebral cortex and down-regulate the mRNA and protein expression of GPx-1. MK-801 can inhibit the expression of Nrf2, HO-1, γ-GCS, GPx-1 expression changes have some antagonism.