母鼠混配农药暴露对仔鼠大脑NMDA受体亚单位NR1表达的影响

目的]探讨母鼠暴露甲基对硫磷与氯氰菊酯混配农药对仔鼠大脑NMDA受体亚单位NR1表达的影响。方法]将48只妊娠Wistar大鼠随机分为高、中、低3个剂量组和1个对照组，于妊娠第1～15天用甲基对硫磷与氯氰菊酯等毒性混配液进行连续灌胃染毒，剂量分别为1／30 LD50、1／95LD50、1／300 LD50，对照组采用食用油灌胃。在仔鼠出生后7、14、21、28天龄时分别从各组中随机抽取5只，共80只动物作为观察对象。采用免疫组化方法测定大脑皮质内侧、皮质外侧、梨状皮质、中脑黑质网状结构、海马（CA1、CA3、DG区）的NR1受体表达。结果]在大脑皮质外侧，中、高剂量组21、28天龄仔鼠的NR1受体蛋白表达比对照组降低（P〈0．05）。在中脑高剂量组21天龄仔鼠的NR1受体表达高于对照组（P〈0．05）。在海马CA1区，高剂量组14天龄仔鼠NR1受体的表达低于低剂量组（P〈0．01），高剂量组21天龄仔鼠则低于对照组和低剂量组（P〈0．01）；随着该混配农药剂量水平的升高，NR1受体蛋白表达显著下降，具有剂量-效应关系（r=-0．377，P〈0．01）。海马CA3区低剂量组14天龄仔鼠的NR1受体阳性细胞表达数高于对照组（P〈0．05），其他部位的NR1受体蛋白表达无改变（P〉0．05）。结论]母鼠甲基对硫磷和氯氰菊酯混配农药暴露可干扰仔鼠脑NR1受体的正常表达过程，使大脑部分区域NR1受体表达下调，延迟受体蛋白的表达高峰。

NR1 Expression at Different Parts of Rat's Brain after Prenatal Exposure to Pesticide Mixture

Objective] To detect expression of NR1 at rat's brain after prenatal exposure to mixed cypermethrion and methylparathion.Methods]48 pregnant rats were divided into four groups randomly.During the gestation of first day to 15th day,all rats were forced fed with mixed pesticides of cypermerthrin plus methyl parathion through garage everyday.The dosage of the two pesticides given to the 4 groups of rats were 0,1/300 LD_(50),1/95 LD_(50),and 1/30 LD_(50),respectively,and vehicle solvent was given to the control group only.At 7,14,21,28 day-old of age,80 rat offspring from 4 groups(5 rats in each age and each group)were sacrificed and different areas of their brains were tested for N-methyl-D-aspartase(NMDA)receptor protein expression with immunohistochemistry,respectively.Results] The positive NR1 cells at outer pallium in 21-day-old and 28-day-old rats of middle and high dosages were lower than that of control group(P<0.05).The expression of NR 1 at region CA 1 of hippocampus in 21-day-old rats of high dose was lower than the control and low dose groups,and there was a dose-response relationship(r=-0.377, P<0.01).In region CA3 of hippocampus,NR1 expression of the 14-day-old rats at low dose group was higher than that of controls (P<0.05).And in reticular-region of diencephalons,NR 1 expression of 21-day-old rats at high dose group was higher than that of controls(P<0.05).There were no differences in NR1 expression in other parts of the brain.Conclusion]Prenatal exposure to mixed cypermethrin plus methyl parathion could affect NR 1 expression in the brain of rat and had lower expression of NR 1 at different parts of the brain.