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目的通过邻苯二甲酸二(2-乙基己基)酯(DEHP)胚胎期暴露,评价其对子代大鼠神经行为的影响,初步探讨DEHP所致子鼠神经毒性的机制。方法雌性Wistar大鼠从妊娠日起用10、100、500 mg/(kg.d)DEHP连续灌胃染毒19 d,观察子代大鼠的神经行为学指标。于子鼠出生第7天和第21天测定海马神经细胞凋亡率,不同剂量的DEHP染毒对海马组织bcl-2、bax基因的表达的影响。结果于子鼠出生6周后,进行水迷宫测试。结果显示,随着DEHP剂量增加,中、高剂量组错误次数增加和潜伏期延长十分明显(F=8.058,P<0.05;F=11.221,P<0.05)。电穿梭测试显示,中、高剂量组电击次数增加和主动逃避时间延长较为明显(F=6.984,P<0.05;F=9.841,P<0.05)。出生后7 d子代大鼠海马神经元的细胞凋亡率高于出生21 d,高剂量组尤为显著。RT-PCR检测表明,与对照组相比,bcl-2和bax基因表达增高(F=253.78,P<0.05;F=66.67,P<0.05),且随着DEHP暴露剂量的升高,表达亦增加。结论 DEHP对子代大鼠神经系统具有明显的毒性作用,存在着剂量-反应关系,其可能通过干扰bcl-2和bax基因的表达而影响子代大鼠神经系统发育。
OBJECTIVE: To evaluate the neurobehavioral effects of DEHP on the neurobehavioral behavior of offspring rats and to explore the mechanism of neurotoxicity induced by DEHP in rats. Methods Female Wistar rats were continuously gavaged with DEHP at doses of 10, 100 and 500 mg / (kg · d) from day gestation for 19 days. The neurobehavioral indexes of offspring rats were observed. The apoptosis rate of hippocampal neurons and the expression of bcl-2 and bax genes in hippocampus after DEHP exposure at different doses were measured on the 7th and 21st day of birth. Results Six weeks after birth, the water maze test was performed. The results showed that with the increase of DEHP dose, the number of errors and prolongation of latency in medium and high dose groups were significantly increased (F = 8.058, P <0.05; F = 11.221, P <0.05). Electroporation tests showed that the number of shocks and the prolongation of active avoidance were significantly increased in the medium and high dose groups (F = 6.984, P <0.05; F = 9.841, P <0.05). The apoptotic rate of hippocampal neurons of offspring in 7 d after birth was higher than that at 21 d of birth, especially in high dose group. The results of RT-PCR showed that the expressions of bcl-2 and bax genes were increased (F = 253.78, P <0.05; F = 66.67, P <0.05) compared with the control group. increase. Conclusion DEHP has a significant toxic effect on the nervous system of offspring rats. There is a dose-response relationship. DEHP may affect the nervous system development of offspring rats by interfering with the expression of bcl-2 and bax genes.