摘要
目的探讨出生后早期有限次数速灭威染毒对ICR小鼠神经发育的影响,尤其是对空间学习记忆能力的影响;同时探讨其可能的毒作用机制。方法小鼠出生第3天开始腹腔注射速灭威(0.05、0.5、5mg/kg),隔天1次,连续6次,DMSO和生理盐水分别为溶剂对照和空白对照。观察一般生理及神经发育情况。末次染毒后24h剖杀一部分,测定脑组织丙二醛(MDA)和还原型谷胱甘肽(GSH)含量。剩余小鼠进行旷场、平衡木、Morris水迷宫等神经行为学测试。结果与溶剂对照比较,高剂量组下牙萌出达标时间略有延迟(约0.5d),各剂量组开眼达标时间均延迟(P<0.01);各剂量组小鼠悬崖回避反射阳性出现时间均延迟(P<0.05),但至青年期在平衡木测试中,各组间已无差异;在旷场实验中,反映自发性活动和焦虑情绪的指标在各组间均无差异性;在Morris水迷宫空间探索实验中,高剂量组小鼠在原平台象限游泳的时间和穿越原隐匿平台次数均减少(P<0.05);各剂量组脑MDA水平显著高于溶剂对照组(P<0.05)。结论出生后早期有限次数接触速灭威可延迟小鼠下牙萌出和开眼这两项生理发育标志的出现,并影响其早期躯体感觉运动功能的发育,感觉运动功能到青年期得以恢复;值得注意的是,出生后早期接触速灭威,将影响到小鼠成年后的空间记忆能力,且可能与氧化应激有关。
Abstract Objective To evaluate the developmental neurotoxicity of low-dose m-tolyl methylcarbamate （MTMC） exposure during postnatal period in mice with emphasis on learning and memory and also its mechanism. Methods ICR mice pups were administered intraperitoneal injections （ip） of MTMC （ DMSO solution, 0, 0. 05, 0.5 and 5.0 mg/kg body weight） or saline every other day from postnatal days （PND） 3 - 13. The general condition and neural development of mice during experiment were evaluated. Parts of mice were killed at 24 h after the last exposure to MTMC for measuring MDA and GSH contents of the cortex. The rest mice were used for neurobehavioral assess- ments which included ： open-field, horizontal bar task, and Morris water maze （MWM）. Results There was a significant delay in eye opening in MTMC-exposure groups and erupting of inferior tooth in the high dose group as com- pared with DMSO control. MTMC-exposure induced reversible effects on sensorimotor activity which were measured by cliff avoidance test （ PND 5 ） and horizontal bar task （ PND 70）. No significant changes in open-field activity were observed. Significant differences in the time in the target quadrant and number of platform-site crossovers in probe trial of MWM test were evident in the MTMC-exposure mice for the high dose group compared to the control group. MTMC-exposure significantly elevated lipid peroxidation in the cortex as compared with DMSO control. Conclusion The results suggest that early postnatal exposure to MTMC affects the physiological growth and developmental neurobehavior in the suckling mice, also affects spatial memory in adult mice. The oxidative stress may be involved in behavioural deficits.
出处
《安徽医科大学学报》
CAS
北大核心
2007年第6期652-657,共6页
Acta Universitatis Medicinalis Anhui
基金
国家自然科学基金(编号:30571585)
安徽省自然科学基金(编号:050430802)
