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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 To evaluate the effects of DEHP on the neurobehavioral development of offspring rats through the embryo exposure of Di-2-ethylhexyl phthalate (DEHP), and to explore the mechanism of denervated neurotoxicity of DEHP . Methods Mature female Wister rats were continuously gavaged with DEHP at doses of 10, 100 and 500 mg / (kg · d) from the gestation day to the point of gestational age 19 d. At the same time, a solvent control group was established. The changes of behavioral teratology and neurobehavioral indexes of offspring were observed. Fura-2 / AM probe was used to detect intracellular Ca2 + concentration in hippocampal neurons 21 days after birth. Results The time-lag was reached in 500 mg / (kg · d) DEHP group and the negative reflex test. The time of reaching the standard in the air inversion experiment in 100 mg / (kg · d) DEHP group and 500 mg / (kg · d) DEHP group was delayed The number of water maze test in each DEHP treatment group increased and the incubation period was prolonged. The number of electroshock tests in electric shuttle experiment increased and the time of active avoidance extended. Compared with the control group, the difference was statistically significant (P <0.05). The intracellular Ca2 + concentration of DEHP in hippocampal neurons increased compared with the control group, and there was a certain dose-effect relationship. Conclusion DEHP embryo exposure may affect the development of the neural system in offspring rats, resulting in neurobehavioral changes. The change of intracellular calcium concentration in hippocampal neurons induced by DEHP may be one of the mechanisms of its neurotoxicity.