慢性铅暴露对小鼠脑海马组织雷帕霉素靶蛋白(mTOR)表达的影响

Effect of chronic lead exposure on expression of mTOR in hippocampus of mice

目的研究慢性铅暴露对小鼠脑海马组织雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）表达的影响，探讨roTOR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^-1，连续42d。对照组鼠饮用自来水。第42天检测血及脑铅浓度，weslem印迹法检测脑海马总量roTOR（t—mTOR）及磷酸化roTOR（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（P〈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（P〈0．05）。p-mTOR表达与血、脑铅浓度呈负相关（r=-0．82，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 study the effect of chronic lead exposure on expression of mammalian target of rapamyein（mTOR） in hippocampus of mice to explore the effect of p-mTOR in learning and memory damage of mice exposed to chronic lead. Methods After mice of 5-6 weeks was mated, newborn mice were exposed to acetic lead（0, 2.4, 4.8, 9.6mmol·L^-1） by placenta, milk and drinking water for 42 days consecutively. The blood and brain lead level was determined by ztomic absorption, the expression of total roTOR （t-roTOR） and phosphorylated mTOR （p-roTOR） determined by Western blot. Results The blood lead and brain lead levels were much higher in lead exposure groups than in control group （ P 〈0.01）. The expression level of p-roTOR in hippocampus of lead exposure groups was decreased significantly compared with normal control group with dose-dependent, and with negative correlation with concentrations of blood lead and brain lead （ r=-0.82, P 〈0.01 ） , but with no change for the t-roTOR protein levels. Conclusion The decreased expression of p-roTOR in hippocampus might be related to the damage of learning and memory induced by lead exposure in mice.