氟、砷染毒对大鼠脑组织CREB mRNA及蛋白表达的影响

Effects of Individual and Combined Exposure to Fluoride and Arsenic on Expression of CREB mRNA and Protein in Rat Brain

  • 摘要:
    目的 探讨氟、砷及其联合染毒对大鼠脑组织中转录因子环磷酸腺苷反应元件结合蛋白(CREB)的影响。

    方法 将32 只初断乳SPF 级雄性SD大鼠随机分为4 组:对照组,氟处理组、砷处理组和联合染毒组,每组8 只。对照组自由饮用蒸馏水,氟、砷处理组和联合染毒组分别自由饮用120 mg/L 氟化钠、70 mg/L 亚砷酸钠、120 mg/L 氟化钠+ 70 mg/L亚砷酸钠水溶液,染毒3 个月。采用实时荧光定量聚合酶链式反应(RT-PCR)方法检测CREB基因mRNA表达水平,蛋白免疫印迹(Western blot)方法检测CREB、磷酸化CREB(p-CREB)的蛋白表达水平。

    结果 氟、砷处理组和联合染毒组大鼠大脑皮质、海马组织CREB mRNA表达水平均明显降低(P < 0.05)。联合染毒组大鼠海马组织CREB mRNA表达水平低于氟、砷处理组(P < 0.05)。氟、砷处理组和联合染毒组大鼠大脑皮质、海马组织p-CREB 的表达水平分别为(0.68& #177;0.16、0.68& #177;0.15)、(0.46& #177;0.13、0.48& #177;0.11)、(0.38& #177;0.11、0.31& #177;0.14),均低于对照组(0.83& #177;0.06、0.80& #177;0.11)(P < 0.05);砷处理组大鼠大脑皮质、海马组织p-CREB 蛋白表达水平均低于氟处理组(P < 0.05);联合染毒组大鼠海马组织p-CREB蛋白表达水平低于氟、砷处理组(P < 0.05)。

    结论 氟、砷及其联合作用可导致大鼠大脑皮质、海马组织CREB基因和磷酸化蛋白表达水平降低。

     

    Abstract:
    Objective To explore the effects of individual and combined exposure to fluoride and arsenic on cAMP response element binding protein (CREB) in brain of rats.

    Methods Thirty-two male Sprague-Dawley rats at the beginning of weaning were randomly divided into 4 groups: 3 groups of rats were exposed to 120 mg/L sodium fluoride (NaF), 70 mg/L sodium arsenite (NaAsO2), or 120 mg/L NaF + 70 mg/L NaAsO2 mixed solution for 90 days, respectively; 1 control group of rats drank distilled water for 90 days. The mRNA expression levels of CREB and protein expression levels of CREB and phosphorylated CREB (p-CREB) in cerebral cortex and hippocampus of rats were detected by real-time polymerase chain reaction and Western blot assay, respectively.

    Results Compared with the controls, the CREB mRNA expression levels in cerebral cortex and hippocampus in the 3 exposure groups were markedly decreased (P < 0.05). The CREB mRNA expression level in hippocampus of co-exposed rats was lower than that in the NaF-exposed or NaAsO2-exposed rats. The p-CREB protein expression levels in cerebral cortex and hippocampus were 0.68& #177;0.16 and 0.68& #177;0.15 respectively for the NaF-exposed rats, 0.46& #177;0.13 and 0.48& #177;0.11 for the NaAsO2-exposed rats, as well as 0.38& #177;0.11 and 0.31& #177;0.14 for the co-exposed rats, respectively; all were significantly lower than those of the controls (0.83& #177; 0.06, 0.80& #177;0.11, respectively) (P < 0.05). Compared with the NaF-exposed rats, the p-CREB protein expression level in cerebral cortex and hippocampus in the NaAsO2-exposed rats were decreased (P < 0.05). The p-CREB protein expression level in hippocampus in the co-exposed rats was statistically lower than that in the NaF-exposed or the NaAsO2-exposed rats (P < 0.05).

    Conclusion Fluoride, arsenic, and co-exposure to both chemicals may down-regulate the expression levels of CREB mRNA and protein phosphorylation in the cerebral cortex and hippocampus of rats.

     

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