孕哺期铅暴露对雄性子代大鼠海马组织中沉默信息调节因子表达的影响

目的探讨大鼠孕期及哺乳期铅暴露对雄性仔鼠海马组织中沉默信息调节因子(silent information regulator1,SIRT1)表达的影响。方法将12只健康SPF级雌性SD孕鼠随机分为3组,分别为对照组(去离子水)、低剂量铅暴露组(0.5 g/L乙酸铅)和高剂量铅暴露组(2.0 g/L乙酸铅),每组4只。采取自由饮水的方式进行染毒,自妊娠第1天开始至仔鼠21 d断乳为止。在仔鼠断乳后,采用电感耦合等离子体原子发射光谱法(ICP-AES)检测6只雄性仔鼠全血和海马组织中铅的含量,采用RT-PCR检测6只雄性仔鼠海马组织SIRT1 mRNA水平的变化,采用Western blot和免疫荧光组织化学法检测6只雄性仔鼠海马组织SIRT1蛋白水平的变化。结果孕哺期不同剂量铅暴露后,雄性仔鼠血铅和海马组织中铅含量均高于对照组,海马中SIRT1 mRNA和蛋白水平的表达均低于对照组,且高剂量铅暴露组仔鼠海马中SIRT1mRNA和蛋白水平低于低剂量组,差异均有统计学意义(P0.05)。结论孕哺期铅暴露可下调仔鼠海马中SIRT1基因表达,从而可能影响海马神经元功能及仔鼠学习记忆能力。

Effect of lead exposure during pregnant and lactation period on expression of SIRT1 in hippocampus of male offspring rats

Objective To explore the effect of lead exposure during pregnant and lactation period on the expression of silent information regulator1 (SIRT1) in hippocampus of male offspring rats.Methods Twelve female SPF grade SD rats were randomly divided into three groups:control group,low and high lead-exposed group,four in each and treated with lead acetate at the doses of 0,0.5 and 2.0 g/L respectively through drinking water from the first day during pregnancy until the 21th day after birth of their offsprings.The contents of lead in blood and hippocampus were determined by inductively coupled plasmaatomic emission spectroscopy (ICP-AES),the level of SIRT1 mRNA in hippocampus was detected with RT-PCR and the changes of SIRT1 protein in hippocampus was detected by Western blot and immunofluorescence histochemistry.Results After exposure to lead at different doses during pregnancy and lactation,the blood lead and hippocampal lead level among male offspring rats were significantly higher compared with the control group (P＜0.05).The level of SIRT1 mRNA and protein in hippocampus in the lead exposed group were significantly lower than that in the control group (P＜0.05),and the levels of SIRT1 mRNA and protein in hippocampus of rats in high dose lead exposure group were lower than those in low dose lead exposure group (P＜0.05).Conclusion Lead exposure in the pregnancy and lactation can reduce the expression of SIRT1 gene in hippocampus of offspring rats,which may affect the function of hippocampal neurons.