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目的:观察F0代孕鼠围产期不同时期双酚A(bisphenol A,BPA)暴露对子代小鼠海马中淀粉样蛋白前体(amyloid precursor protein,APP)、微管相关蛋白(microtubule-associated protein,Tau)、磷酸化的Tau蛋白(p-Tau)的影响,探讨雌雄小鼠胎儿发育阶段BPA暴露的敏感期。方法:利用C57BL/6J胎鼠原代培养的海马神经元共孵BPA;F0代小鼠围产期皮下注射建立BPA暴露小鼠模型,根据不同暴露期分为4组,即对照组、胎儿期(P6-PND0)、哺乳期(PND0-PND21)、胎儿期和哺乳期联合暴露(P6-PND21),取其成年子代海马组织(8月龄)通过Western blot方法检测APP、Tau及p-Tau的表达量。结果:海马神经元细胞与不同浓度BPA共孵后,APP、Tau及p-Tau的表达均上调,呈剂量依赖性。BPA连续暴露后的子代小鼠中,雌性小鼠PND0-PND21组、P6-PND21组海马组织中APP、Tau及p-Tau表达增加,而雄性小鼠仅P6-PND21组3种蛋白的表达上调。结论:围产期BPA连续暴露可引起子代小鼠海马APP、Tau及p-Tau表达改变,从而可能引起神经损伤,而雌性小鼠相较于雄性小鼠可能对BPA引起的神经损伤更敏感。
Objective: To investigate the effects of exposure to bisphenol A (BPA) on the expression of amyloid precursor protein (APP), microtubule-associated protein , Tau), phosphorylated Tau protein (p-Tau), to explore the sensitive period of BPA exposure in the male and female fetus during fetal development. Methods: Primary cultured hippocampal neurons of C57BL / 6J fetus were used to incubate BPA. BPO-exposed mouse models were established by perinatal subcutaneous injection in F0 generation mice. According to different exposure periods, they were divided into 4 groups: control group, (P6-PND0), lactation (PND0-PND21), fetal and lactation combined exposure (P6-PND21). The hippocampus tissues of adult children (8 months old) Tau expression levels. Results: After incubation with different concentrations of BPA, the expression of APP, Tau and p-Tau were up-regulated in a dose-dependent manner. In the offspring mice exposed to BPA continuously, the expression of APP, Tau and p-Tau in hippocampus of PND0-PND21 group and P6-PND21 group were increased in female mice, but only in P6-PND21 group Increase. CONCLUSION: Continuous exposure of perinatal BPA can cause altered expression of APP, Tau and p-Tau in the hippocampus of offspring, which may result in nerve injury, while female mice may be more sensitive to BPA-induced nerve injury than male mice .