塑化剂DEHP对子代大鼠神经毒性机制探讨  

Effect on the nervous behavioral development after embryonic exposure to DEHP in offspring rats

作　　者：李丹丹[1] 刘尚辉[2] 潘亮[1] 于涛[1] 刘艳华[1] 刘秋芳[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 [2]中国医科大学计算机教研室

出　　处：《毒理学杂志》2012年第5期326-330,共5页Journal of Toxicology

基　　金：辽宁省教育厅科学技术项目(L2010703)

摘　　要：目的通过塑化剂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神经发育毒性机制,为其安全性评价提供科学依据。方法成熟雌性Wistar大鼠从妊娠日起用10、100和500 mg/(kg.d)DEHP连续灌胃染毒19 d,动态观察子代大鼠的自然状况、体重变化和神经行为学指标变化。提取海马组织的总RNA,逆转录合成cDNA。RT-PCR扩增后分别比较不同剂量的DEHP染毒对海马组织StAR、CYP19A1基因转录的影响。结果于子鼠出生6周后,进行水迷宫测试,随着DEHP剂量增加,与对照组相比,在中、高剂量组错误次数增加和潜伏期延长尤为明显,且均有统计学意义(F=8.058,P<0.05;F=11.221,P<0.05);电穿梭测试时,与对照组相比,同样在中、高剂量组电击次数增加和主动逃避时间延长尤为明显,且均有统计学意义(F=6.984,P<0.05;F=9.841,P<0.05)。RT-PCR检测表明,与对照组相比,CYP19A1基因转录水平有统计学意义(F=6.083,P<0.05),且随着DEHP暴露剂量的升高,CYP19A1基因转录水平降低,而StAR基因转录水平在各组间差别不明显。结论 DEHP对子代大鼠神经系统发育具有明显的毒性作用,且存在着剂量-反应关系;DEHP及其代谢产物可能通过干扰神经类固醇CYP19A1芳香化酶基因的转录而影响子代大鼠神经系统发育。Objective To study the effects on nervous behavioral development in offspring of rats exposed to DEHP during pregnancy, and provide some basic data for the further study of development neurotoxicity induced by DEHP. Methods The mature female Wistar rats were lavaged consecutively with the DEHP dose of 10,100 and 500 mg/（kg-d） from the first day until the 19th day of pregnancy. The general situation of pregnant rats and the birth rate were observed dynamically. After the offspring rats were born, the changes of body weight and the nervous behavior indexes in the offspring rats were observed. The total RNA in hippocampus was extracted and cDNA synthesis was followed as the manual instruction of RT-PCR kit. The effects of DEHP on gene transcription of StAR and CYP19A1 were analyzed in DEHP exposed groups and the control. Results After birth of six weeks, in water maze experiment , both false times and latency increased in as a dose-dependent way, especially for 100 and 500 mg/（ kg· d） groups （ F = 8. 058, P 〈 0.05 ; F = 11. 221, P 〈 0. 05）. Meanwhile, for electricity shuttled test, both shocked times and active elusion time prolonged in the DEHP dose groups, 100 and 500 mg/（ kg· d） groups showed significantly （ F = 6. 984, P 〈 0.05 ; F = 9. 841, P 〈 0. 05 ）. In addition, the distinct difference in the gene transcription of StAR wash＇ t shown in the study. However, there were a remarkable decrease between DEHP exposed groups and the control in the gene transcription of CYP19A1 in hippocampus, especially for the 500 mg/（ kg·d） group （ F = 6. 083, P 〈 0. 05 ）. The gene transcription of CYP19A1 decreased with the increasing dose of DEHP. Conclusion DEHP could have an influence on the transcription of aromatized enzyme such as CYP19A1 , and then induce nervous toxicity on offspring rats during the developmental phase.

关 键 词：塑化剂DEHP 神经行为学 神经类固醇 STAR CYP19A1 

分 类 号：R114[医药卫生—卫生毒理学]