毒死蜱低剂量重复染毒致学习记忆功能障碍及CREB信号途径的抑制(Repeated Exposures to Low-Level Chlorpyrifos Result in Learning Memory Impairment and Inhibition of the CREB Signal System)

毒死蜱(CPF)是我国推荐使用的低毒有机磷农药之一,目前在全世界广泛应用.选择不引起动物出现全身系统毒性的CPF剂量(1、5、10mg·kg-1)对大鼠连续染毒4周,评价CPF对动物的学习记忆功能和CREB信号通路的影响.结果显示:CPF连续染毒后动物出现记忆能力的损伤,随着染毒剂量的增加,海马、皮质和纹状体CREB及ERKI/Ⅱ磷酸化蛋白表达逐渐减少,这表明ERK/CREB信号通路可能是参与毒死蜱低剂量重复暴露致学习记忆功能改变的重要途径.

Repeated Exposures to Low-Level Chlorpyrifos Result in Learning Memory Impairment and Inhibition of the CREB Signal System

Chlorpyrifos is one of the commonly used insecticides through the world,which is recommended as the substitute for methamidophos or parathion in agriculture in China.The purpose of this study is to evaluate the learning memory changes and CREB signal systems involved repeated,low-level doses of CPF in rats.In the present study,male Wistar rats were given 0,1.0,5.0 or 10.0mg·kg-1·d-1 of CPF through intragastric administration daily for 4 weeks.Performance in the learning tasks was impaired after 28d of exposure to CPF(24h after the last dosage).The phosphorylated protein expression of ERKI/II and CREB decreased.Our results indicates that ERK/CREB signal system may be the important pathway to regulate the CPF caused learning memory deficit.