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目的研究慢性铅暴露对小鼠脑海马组织雷帕霉素靶蛋白(mammaliantargetofrapamycin,mTOR)表达的影响,探讨mTOR在慢性铅暴露所致小鼠海马神经元学习记忆功能障碍中的作用。方法 5~6周龄小鼠交-1配后,铅暴露组仔鼠通过胎盘、乳汁和饮水饲醋酸铅2.4,4.8和9.6mmol·L,连续42d。对照组鼠饮用自来水。第42天检测血及脑铅浓度,Western印迹法检测脑海马总量mTOR(t-mTOR)及磷酸化mTOR(p-mTOR)的表达。结果各慢性染铅组小鼠血铅和脑铅含量均明显高于对照组(<0.01),升高的程度与饮用水的铅浓度呈正相关。慢性染铅组小鼠大脑海马组织p-mTOR表达水平呈下降趋势,各染铅组p-mTOR表达与对照组比较,差异有统计学意义,并具有浓度效应关系(<0.05)。p-mTOR表达与血、脑铅浓度呈负相关(r=-0.82,铅对小鼠大脑皮层神经元t-mTOR的磷酸化没有影响。结论 p-mTOR蛋白的表达量随着铅暴露的浓度升高而降低,与铅致小鼠学习记忆功能减退有关。P P P<0.01),铅对小鼠大脑皮层神经元t-mTOR的磷酸化没有影响。结论 p-mTOR蛋白的表达量随着铅暴露的浓度升高而降低,与铅致小鼠学习记忆功能减退有关。
Objective To investigate the effect of chronic lead exposure on the expression of mammalian cerebral myocyte target protein (mTOR) in mice hippocampus and to explore the role of mTOR in learning and memory dysfunction induced by chronic lead exposure in hippocampal neurons of mice. Methods After 5 to 6 weeks of age, the lead exposed pups were fed with 2.4, 4.8 and 9.6 mmol·L of lead acetate through the placenta, milk and drinking water for 42 days. Control mice drinking tap water. Blood and brain lead concentrations were measured on the 42nd day. The total hippocampal levels of mTOR (t-mTOR) and phosphorylated mTOR (p-mTOR) were detected by Western blotting. Results The levels of blood lead and brain lead in mice with chronic lead exposure were significantly higher than those in the control group (<0.01). The level of blood lead was positively correlated with the lead concentration in drinking water. The expression of p-mTOR in hippocampus of chronic lead-exposed mice showed a decreasing trend. The expression of p-mTOR in each lead-exposed group was significantly different from that in control group (P <0.05). The expression of p-mTOR was negatively correlated with blood lead and brain lead concentration (r = -0.82, Pb had no effect on the phosphorylation of t-mTOR in mouse cerebral cortical neurons.Conclusion The expression of p-mTOR protein decreases with the concentration of lead exposure (P <0.01). Lead had no effect on the phosphorylation of t-mTOR in mouse cerebral cortical neurons. Conclusion The expression of p-mTOR protein decreases with the increase of lead exposure, which is related to the decline of learning and memory in lead-induced mice.