邻苯二甲酸二(2-乙基)己酯(DEHP)胚胎期暴露对子代大鼠神经行为发育的影响  

Effects on neurobehavioral development in offspring rats after embryonic exposure to di-2-ethylhexyl phthalate(DEHP)

作　　者：刘艳华[1] 刘秋芳[1] 潘亮[1] 于涛[1] 肖莎[1] 逯晓波[1] 

机构地区：[1]中国医科大学公共卫生学院卫生毒理教研室,辽宁沈阳110001

出　　处：《毒理学杂志》2011年第6期414-417,共4页Journal of Toxicology

基　　金：辽宁省教育厅科学技术项目(L2010703)

摘　　要：目的通过邻苯二甲酸二(2-乙基)己酯(Di-2-ethylhexyl phthalate,DEHP)胚胎期暴露,评价DEHP对子代大鼠神经行为发育的影响,初步探讨DEHP的发育神经毒性机制。方法成熟雌性Wister大鼠从妊娠日起用10、100和500 mg/(kg.d)DEHP连续灌胃染毒至孕19 d,同时设立溶剂对照组。观察仔鼠的行为畸胎学及神经行为学指标的改变,另外Fura-2/AM探针法检测出生后21 d海马神经元细胞内Ca2+浓度变化。结果 500 mg/(kg.d)DEHP组与负趋地性反射实验达标时间延迟;100 mg/(kg.d)DEHP组、500 mg/(kg.d)DEHP组空中翻正实验达标时间延迟;各DEHP染毒组水迷宫实验错误次数增加,潜伏期延长;电穿梭实验电击次数增加、主动逃避时间延长,与对照组相比,差异有统计学意义(P<0.05)。对于海马神经元细胞内Ca2+浓度DEHP各染毒组与对照组相比升高,并且存在一定剂量效应关系。结论 DEHP胚胎期暴露可影响子代大鼠神经系统发育,造成神经行为学改变。DEHP所致海马神经元细胞内钙离子浓度的改变可能为其发育神经毒性的机制之一。Objective Our purpose is to evaluate the effects of Di-2-ethylhexyl Phthalate （DEHP） on the development of central nerve system and neuro behavior in offspring by embryonic exposure and to explore the mechanism of DEHP developmental neurotoxicity. Methods The female Wistar rats were gavaged consecutively with the DEHP dose of 0 mg/（ kg· d） , 10 mg/（kg·d） , 100 mg/（ kg· d） and 500 rag/（ kg· d） from pregnancy day 1 to 19. After the offspring were born, the changes of behavior teratology and neurobehavioral and Ca^2 ＋ concentration of hippocampus neurons cells on PND 21 were observed. Results The time of 500 mg/（kg·d） DEHP group was shorter than that of the control group on negative geotaxis reflection experiment, the time of 100 mg/（kg· d） and 500 mg/（kg·d） DEHP groups were longer than control group on Air righting reflex. The difference was statistically significant （P 〈 0. 05）. The difference of error times and incubation period were found in DEHP-treated groups compared with the control group; Electric shock times increasing and active escape time prolong in the DEHP-treated groups compared to the control group. Both the differences were statistically significant （ P 〈 0. 05 ）. The [ Ca^2＋ ] concentrations of the DEHP-treated groups were increasing significantly compared with control group and there was a certain dose- response relationship. Conclusion After embryonic exposure to DEHP the develop mental toxicity of rat offsprings appeared. The changes of [ Ca^2＋ ] concentration may be mechanism of DEHP developmental neurotoxicity.

关 键 词：邻苯二甲酸二(2-乙基)己酯(DEHP) 发育神经毒性 神经行为学 Ca2+浓度 

分 类 号：R114[医药卫生—卫生毒理学]