目的探讨出生前后镧暴露对子代大鼠海马环磷酸腺苷反应元件结合蛋白(CREB)磷酸化水平、脑源性神经营养因子(BDNF)mRNA及蛋白表达影响。方法60只Wistar雌性大鼠随机分为对照组和低、中、高剂量镧染毒组,各镧染毒组从雌鼠受孕日起到子鼠断乳后1个月通过自由饮水方式染毒,测定海马p-CREB、BDNFmRNA和蛋白表达水平。结果与对照组比较,低、中、高剂量染镧组子代大鼠海马P—CREB蛋白表达水平分别为(0.77±0.063)、(0.62±0.057)、(0.52±0.051)、BDNFmRNA表达水平分别为(0.80±0.072)、(0.56±0.090)、(0.41±0.075)及BDNF蛋白表达水平分别为(0.67±0.065)、(0.59±0.064)、(0.51±0.045)均下降(P〈0.05)。结论镧可以抑制大鼠海马CREB磷酸化和BDNF基因转录及蛋白表达。
Objective To study the effects of perinatal lanthanum exposure on cAMP response element binding pro- tein phosphorylation (p-CREB) and brain derived neurotrophic factor (BDNF) mRNA and protein expression in the hip- pocampus of offspring rats. Methods Sixty female Wistar rats were divided randomly into control, low-, medium-, and high-dose lanthanum-treated group. Rats in lanthanum-treated groups were administrated with 0. 25 % ,0. 5 % , and 1% lan- thanum chloride ( LaC13 ) in drinking water from day 0 of pregnancy to one month after weaning of the offspring,respec- tively. Then the p-CREB,BDNF mRNA and protein expression in the hippocampus were measured. Results Compared to the control group,hippocampal p-CREB protein expressions were 0. 77 ± 0. 063,0. 62 ± 0. 057 and 0. 52 ± 0. 051 ;the BDNF mRNA expressions were 0. 80 ± 0. 072,0. 56 ±0. 090,and 0.41 ±0. 075 and the BDNF protein expressions were 0. 67 ± 0. 065,0. 59 ± 0. 064,and 0. 51 ± 0. 045 for 0. 25% ,0. 5% ,and 1% lanthanum-treated offspring, respectively, with significant decreases ( P 〈 0. 05 ). Conclusion Perinatal lanthanum exposure could decrease CREB phosphorylation and BDNF gene transcription and protein expression in the hippocampus of rats.