甲基汞对大鼠的行为致畸效应研究

Effects of neurobehavioral teratogenicity in Wistar rats after pregnant exposure to methylmercury

目的 探讨妊娠期甲基汞暴露对Wistar大鼠的母体毒性及仔代的行为致畸效应。方法 Wistar孕鼠80只于妊娠第 6～ 9天采用甲基汞 0 0 0、0 0 1、0 0 5和 2 0 0mg·kg- 1 ·d- 1 连续灌胃染毒。分别进行母体毒性、胚胎毒性、仔鼠早期生理发育和神经行为发育指标、仔鼠迷宫和程序控制行为测试、亲仔两代大鼠脑组织形态学观察和单胺类神经递质 (去甲肾上腺素、多巴胺、5 羟色胺 )的测定。整个实验采用双盲法。结果 未观察到明显的母体毒性 ;3个剂量组胎仔的体重、尾长均低于对照组 (P <0 0 1) ;各剂量组仔鼠的体重增长、早期生理及神经行为发育滞后于对照组 (P <0 0 5 ) ;各剂量组仔鼠迷宫错误次数均比对照组多 (P <0 0 5 ) ,具有剂量 效应关系 (rs=0 .2 5 7,P <0 0 5 ) ;程序控制行为学习成绩比对照组降低 (P <0 0 5 ) ,有剂量 效应关系 (rs=- 0 .72 73,P <0 0 1) ;各剂量组母鼠和仔鼠脑组织均未见形态学改变 ,但脑组织单胺类神经递质含量均比对照组明显增高 (P <0 0 5 ) ,有剂量 效应关系 (rs=0 .712 4～ 0 92 5 7,P <0 0 1)。结论 甲基汞在不引起可观察到母体毒性剂量下 ,就可产生胚胎毒性 ,影响仔鼠神经系统的发育 ,导致神经行为功能的改变。

Objective To detect effects of maternal toxicity and behavioral teratogenicity in offspring of Wistar rats after pregnant exposure to methylmercury.Methods Methylmercury was force fed to 80 pregnant Wistar rats from the sixth day to ninth day after conception, with doses of 0.00,0.01,0.05 and 2.00 mg\5kg -1 \5d -1 .The toxicity both in maternal rats and embryos was measured.The developing landmarks of 205 offspring were measured.The maze test of 79 offspring and operant behavior test of 32 offspring were carried out at the age of 7 or 10 weeks,respectively.The brain's morphology and the levels of monamine neurotransmitter were tested in 24 maternal rats after 5 weeks of the delivery and 24 offspring in 10 weeks old.Double blind test was used in whole experiment.Results The body weight and tail development of embryos in 3 exposure groups were slower those of control group ( P <0 01).The developing landmarks and neurobehavioral development of offspring in 3 exposure groups were delayed than of control groups ( P <0 05);their performances in Y maze and operant behavior were worse than those of control group ( P <0 05).No histomorphological alterations in brains of dam and offspring were observed in all groups.The levels of monamine neurotransmitter in both dam's and offspring's brains in 3 exposure groups were increased than those of control groups ( P <0 05).Conclusion Prenatal exposure to methylmercury showed some embryotoxicity and adverse effects in the developing nervous system,which resulted in neurobehavioral changes in rat offspring.