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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(P<0.05)。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。
Objective To investigate the effect of lead exposure during pregnancy and lactation on the expression of silent information regulator1 (SIRT1) in male offspring hippocampus. Methods Twelve healthy pregnant SDF pregnant rats were randomly divided into three groups: control group (deionized water), low dose lead exposure group (0.5 g / L lead acetate) and high dose lead exposure group (2.0 g / L lead acetate), 4 in each group. Take a free drinking water exposure, since the first day of pregnancy until the offspring of 21-day pups so far. The levels of lead in whole blood and hippocampus of 6 male offspring rats were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES) after the offspring of offspring were weaned. The levels of SIRT1 The level of SIRT1 protein in hippocampus of 6 male offspring rats was detected by Western blot and immunofluorescence staining. Results Lead levels in blood lead and hippocampus of male offspring rats were significantly higher than those of the control group at different doses of lead exposure during pregnancy and lactation. The expression of SIRT1 mRNA and protein in the hippocampus was lower than that in the control group. The hippocampal SIRT1 mRNA and protein levels were lower than the low dose group, the difference was statistically significant (P <0.05). Conclusion Lead exposure during pregnancy and lactation can down-regulate the expression of SIRT1 gene in the hippocampus of the offspring, which may affect the function of hippocampal neurons and the learning and memory ability of the offspring.