大鼠一次性经皮染毒毒死蜱的毒代动力学和毒效应学研究  

Toxicokinetics and toxicodynamics of chlorpyrifos in rats following one single subcutaneous exposure

作　　者：赵敏娴[1] 姚欣雅[1] 曹正颖 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：《癌变．畸变．突变》2015年第2期129-133,共5页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：国家自然科学基金(81273080;81072304)

摘　　要：目的：研究大鼠一次性经皮染毒毒死蜱（CPF）的毒代动力学和毒效应学特征。方法：成年雌性SD大鼠按体质量随机分成3个剂量组（69．75、139．5、279mg／kg）和1个对照组（0 mg／kg），皮下注射染毒，各组在给药后3、6、12、24、48、72h共6个时间点收集大鼠血液和大脑皮质样本，在0～24、0～48和0—72h连续收集尿液样本。测定指标包括血清CPF浓度，血清和尿液3，5，6-三氯-2-吡啶（TCP）浓度以及血清和大脑皮质乙酰胆碱酯酶（ACHE）活性。结果：经皮染毒CPF剂量越大，大鼠血清CPF和TCP浓度越高，尿TCP排出量越大，血和皮质AChE活性抑制越大；血清CPF浓度在6h达峰值，血清TCP浓度在12～24h达峰值，血AChE活性在24h最低，大脑皮质AChE活性在24～48h最低。各剂量组血清CPF的半衰期为29—48h，0～72h曲线下面积（AUC）为31—110h·μmol／L；血清TCP的半衰期为28～54h，0～72h AUC值为897—3450h·μmol／L。血AChE活性和大脑皮质AChE活性呈正相关（P〈0．01），且血中的抑制率大于大脑皮质（P〈0．01）。用Dose Resp函数拟合血清CPF和AChE活性，呈现出剂量反应关系。结论：CPF外暴露剂量与大鼠体内CPF、TCP和AChE活性相关，内暴露水平和血AChE活性存在剂量效应关系；尿TCP排出量可作为机体暴露水平的生物标志；血AChE活性是大脑皮质AChE活性的有效生物标志。OBJECTIVE： In this study, the toxicokinetics and toxicodynamics of chlorpyifos were assessed in rats following one single subcutaneous exposure. METHODS： Adult female SD rats, randomly divided into three dose groups （69.75, 139.5, 279 mg/kg） and one control group （0 mg/kg）, received one subcutaneous injection.Blood and cerebral cortex samples were collected on 3, 6, 12, 24, 48 and 72 hours in each group, and 0-24, 0-48, 0-72 h urine samples were collected continuously. The indicators included chlorpyrifos （CPF） in serum, 3, 5, 6-trichloro-2- pyridyol （TCP） in urine and serum, and acetylcholinesterase （ACHE） in serum and cortex. RESULTS： With the increase in the exposure dose, the concentration of serum CPF, serum TCP, urine TCP and inhibition of serum and cortex AChE increased. The peak concentration of serum CPF and TCP were 6 and 12-24 h, respectively. Maximum inhibition of serum and cortex AChE occured at 24 and 24-48 h, respectively. Half-life（t1/2） of serum CPF was 29-48 h, and 0-72 h area under the curve （AUC） was 31-110 h · μmol/L in each group, t1/2 of serum TCP was 28-54 h, and 0-72 h AUC value was 897-3 450 h · μmol/L. Serum and cortex AChE activity demonstrated a positive correlation （P〈0.01）, and serum AChE activity had higher inhibition （P〈0.01）. There was a dose-response relationship between serum CPF and ACHE, fitting by DoseResp curve. CONCLUSION： External exposure dose of CPF was correlated with CPF, TCP and AChE activity. There was a dose-effect relationship between CPF internal level and serum AChE activity. Excretion of TCP in urine can be used as a biomarker of exposure. Serum AChE activity was an effective biomarker of cortex AChE activity.

关 键 词：毒死蜱 3 5 6-三氯-2-吡啶 乙酰胆碱酯酶 毒代动力学 毒效应学 

分 类 号：R969.1[医药卫生—药理学]