大鼠急性经口暴露毒死蜱的毒物代谢动力学和毒物效应动力学研究  

Toxicokinetics and toxicodynamics of chlorpyifos in rats with single oral gavage exposure to chlorpyrifos

作　　者：吴惠[1] 乙楠楠[1] 刘沛[1] 李亭亭[1] 何贤松[1] 赵敏娴[1] 姚欣雅[1] 王灿楠[1] 

机构地区：[1]东南大学公共卫生学院环境医学工程教育部重点实验室,东南大学公共卫生学院营养与食品卫生系,江苏南京210009

出　　处：《南京医科大学学报（自然科学版）》2014年第5期592-596,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金资助(81273080);教育部博士点基金资助(2010009211052)

摘　　要：目的：测定一次性经口暴露毒死蜱（chlorpyrifos,CPF）的毒物代谢动力学和毒效学指标,研究CPF的毒代动力学和毒效学特征。方法：雌性SD大鼠按体质量随机分为4个剂量组和1个阴性对照组,每组15只。剂量分组为：12.5、25.0、50.0、100.0 mg/kg,一次性灌胃染毒。染毒后1、3、6、12和24 h 5个时间点分别在每个剂量组随机选择3只大鼠,乙醚麻醉,股动脉取血,颈椎脱臼处死,分离大脑皮质,用高效液相色谱法测定这5个时间点的血清中CPF和3,5,6-三氯-2-吡啶（3,5,6-trichloropyridinol,TCP）的浓度,用胆碱酯酶试剂盒测定血清和大脑皮质中乙酰胆碱酯酶（acetylcholinesterase,AChE）活性。结果：血清CPF和TCP的浓度随时间变化,先上升后下降,前者峰值浓度出现在染毒后3 h,后者为6 h左右;血清和皮质的AChE活性随时间变化,先下降后上升,血清AChE活性在染毒后3－6 h抑制程度最大,皮质AChE在染毒后6－12 h抑制程度最大。血清CPF浓度。TCP浓度与AChE活性均成线性负相关,血清CPF浓度与TCP浓度呈线性正相关。结论：获得了毒死蜱经口暴露的多项毒代动力学和毒效学数据,阐明了毒代动力学和毒效学特征,为毒死蜱生理毒物代谢动力学和毒物效应动力学模型的建立和完善提供了科学依据。Objective：To measure the index of toxicokinetics and toxicodynamics of chlorpyifos in Sprague-Dawley rats after single oral-dose exposure to chlorpyrifos（CPF）,and study the characteristic of toxicokinetics and toxicodynamics of CPF. Methods：The adult female SD rats were randomly divided into 5 groups （including 1 control group and 4 treated groups） according to the weight. Each group has fifteen rats. The dose of chlorpyrifos is respectively 12.5 mg/kg,25 mg/kg,50 mg/kg,100 mg/kg. Blood samples were collected through arteria cruralis after single dose gastric gavage exposure at 1 h,3 h,6 h,12 h,and 24 h,then rats were killed and cortexes were collected. The concentrations of CPF and TCP（3,5,6-trichloropyridinol）at every five time point in plasma were determined by HPLC（high performance liquid chromatography）,and acetylcholinesterase（AChE） activity was estimated by the Pureauto CHE. Results：The peak concentration of CPF and TCP first peak were observed at 3 h and 6 h,respectively,then declined. The maximum inhibition of plasma AChE was observed between 3 to 6 h. Maximum inhibition of cortex AChE occurred between 6 to 12 h. Both the plasm concentration of CPF and TCP were linear negatively correlated with the plasm AChE activity. The plasm concentration of CPF and TCP showed a linear positive correlation. Conclusion：Through this study,we obtain several indexes of toxicokinetics and toxicodynamics of CPF,and represent the characteristics. These results will provide useful information to the physiologically based toxicokinetics and toxicodynamics（PBTK/TD）model.

关 键 词：毒死蜱 毒物代谢动力学 毒物效应动力学 

分 类 号：R114[医药卫生—卫生毒理学]