甲基汞对亲仔两代大鼠的神经行为毒性效应

Maternal Toxicity and Offspring Neurobehavioral Effects in Wistar Rats Induced by Exposure to Methylmercury During Pregnancy

目的探讨大鼠妊娠期甲基汞暴露的母体毒性及对仔代的神经行为毒性效应。方法Wistar孕鼠52只于妊娠第6～9天用甲基汞0.00、0.01、0.05、2.00mg/(kg·d)连续灌胃。分别观察母体毒性 ;常规致畸实验 ;记录205只仔鼠早期生理发育和神经行为发育指标 ;10周龄仔鼠32只进行程序控制行为测试 ;分娩后5周母鼠和10周龄仔鼠各24只进行脑组织形态学观察和单胺类神经递质的测定。实验遵循随机、双盲原则。结果未观察到母体毒性和仔代形态畸形 ;3个暴露组胎仔的体重、尾长低于对照组 (P<0.01) ;各暴露组仔鼠体重增长、早期生理及神经行为发育滞后于对照组 (P<0.05) ;程序控制行为学习成绩比对照组降低 (P<0.05) ,有剂量_效应关系 (rs= -0.7273 ,P<0.01) ;各暴露组母鼠和仔鼠脑组织无形态学改变 ,但单胺类神经递质含量均比对照组显著增高 (P<0.05) ,有剂量_效应关系 (rs=0.7124～0.9257 ,P<0.01)。结论本研究剂量的妊娠期甲基汞暴露未观察到对孕鼠的毒性效应 ,但有轻度胚胎毒性 ,影响仔鼠的神经系统发育 ,导致仔鼠学习记忆能力降低 。

Objective To explore the maternal toxicity and offspring's neurobehavioral effects in Wistar rats induced by exposure to methylmercury during pregnancy. Methods Methylmercury were continuously orally perfued with different doses of 0.00, 0.01, 0.05 and 2.00 mg/(kg·d) to 52 pregnant Wistar rats during the 6th～9th day after conception. The toxicity to maternal rats was observed and general teratology test were carried out. The parameters of physical and neurobehavioral develpment at early stage of 205 offspring were measured and the operant behavior test of 32 offspring was carried out at the age of 10 weeks. 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 randomized design was used in whole experiment. Results No maternal toxicity and offspring teratogenicity were observed. The increase of body weight and tail development of embryos in 3 exposure groups were slower than those of control group (P<0.01). The developing landmarks and neurobehavioral development of offspring in 3 exposure groups were delayed than those of control group (P<0.05). The offspring performances in operant behavior test were worse than control group (P<0.05), and revealed a dose_effect relationship (rs=-0.7273, P<0.01). No histomorphological alterations in brains of dam or offspring were observed in all groups. The levels of brains' monamine neurotransmitter both in dam and offspring of 3 exposure groups were increased than those of control groups (P<0.05), and also revealed dose_effect relationships (rs=0.7124～0.9257, P<0.01). Conclusion Methylmercury exposure during pregnancy showed no matornal toxicity,but slight embryotoxicity, adverse effects in the developing nervous system, it resulted in neurobehavioral changes with the dose range given in this study in rat offspring and increasing the levels of brains monamine neurotransmitter in dam and offspring.