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[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120mg/L氟化钠、70mg/L亚砷酸钠、120mg/L氟化钠+70mg/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±0.16、0.68±0.15)、(0.46±0.13、0.48±0.11)、(0.38±0.11、0.31±0.14),均低于对照组(0.83±0.06、0.80±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。
[Objective] To investigate the effects of fluoride, arsenic and their combination on the transcription factor cyclic adenosine monophosphate response element binding protein (CREB) in rat brain. [Method] Thirty-two primordial SPF male SD rats were randomly divided into 4 groups: control group, fluoride treatment group, arsenic treatment group and combination exposure group, with 8 rats in each group. In control group, drinking distilled water, fluoride, arsenic treatment group and joint exposure group were free to drink 120mg / L sodium fluoride, 70mg / L sodium arsenite, 120mg / L sodium fluoride + 70mg / L sodium arsenite solution, Toxic for 3 months. The mRNA expression of CREB gene was detected by real-time fluorescent quantitative polymerase chain reaction (RT-PCR). The protein expression of CREB and phosphorylated CREB (p-CREB) was detected by Western blot. [Result] The CREB mRNA expression levels in cerebral cortex and hippocampus were significantly decreased in fluoride, arsenic-treated and combination groups (P <0.05). The level of CREB mRNA expression in the hippocampus of the joint exposure group was lower than that of the fluoride and arsenic treatment groups (P <0.05). The expression levels of p-CREB in the cerebral cortex and hippocampus were (0.68 ± 0.16,0.68 ± 0.15), (0.46 ± 0.13,0.48 ± 0.11), (0.38 ± 0.11, 0.31 ± 0.14), which were lower than those in the control group (0.83 ± 0.06,0.80 ± 0.11) (P <0.05). The expression of p-CREB protein in cerebral cortex and hippocampus in arsenite-treated group was lower than that in the fluoride-treated group 0.05). The expression level of p-CREB protein in hippocampus of rats in combined exposure group was lower than that in fluoride and arsenic treatment groups (P <0.05). [Conclusion] Fluorine, arsenic and their combined effects can decrease the expression of CREB gene and phosphorylated protein in the cerebral cortex and hippocampus of rats.