大鼠动态吸入氯吡硫磷染毒模型的建立及致伤效应评价

摘要

目的：建立大鼠全身暴露动态吸入有机磷农药氯吡硫磷（CPF）的染毒模型，探讨SD大鼠急性吸入CPF致伤效应。方法通过优化气溶胶发生参数，建立大鼠急性吸入CPF的动态暴露环境；利用吸附采样-气相检测技术监测暴露舱内CPF的浓度，利用粒径监测仪实时监测暴露舱内CPF的粒径，同时考察气溶胶的浓度和粒径随时间的变化；采用Bliss法，将SPF级雄性SD大鼠置于染毒环境中进行染毒，在不同浓时积（Ct）下观察染毒过程中大鼠的症状，记录染毒后各浓度组大鼠10 d内的死亡情况；同时根据半数致死Ct （LCt50），检测不同暴露浓度染毒后不同时间点血浆胆碱酯酶（ChE）活性变化。结果暴露舱内CPF气溶胶浓度在9个时间段的平均值为160.6 mg·m-3，变异系数（RSD）为6.9%；气溶胶粒径几何平均值为1.1μm，几何标准偏差为1.8，符合国际经济合作与发展组织急性吸入染毒技术要求。在此染毒条件下，SD大鼠全身暴露动态吸入染毒的LCt50为1654.2 mg·m-3·h，随着染毒浓度的增加，血浆ChE活性抑制愈加明显（P<0.05）。结论本研究成功建立了大鼠全身暴露动态吸入CPF染毒模型，为有机磷类工农业产品以及神经性毒剂吸入致伤和防治研究提供实验平台和技术支撑。%OBJECTIVE To establish a model for chlorpyrifos(CPF)whole-body dynamic inhalation exposure in SD rats and investigate the injury effects after acute exposure by CPF. METHODS By optimizing the aerosol parameters ,the animal acute dynamic inhalation exposure of CPF was established. Absorption sampling-gas phase detecting technology was used to monitor the concentration of CPF in the whole-body dynamic-inhalation exposure cabin by exploring the relationship between the concentration , particle size of CPF aerosol and the CPF inhalation time in the exposure cabin via a particle size detector. Using Bliss method,specific pathogen free SD male rats were allocated to the environment of CPF exposure at different lethal concentrations and time points. The symptoms and deaths of these SD male rats in different groups were recorded within the following 10 d. Based on the median lethal concentra⁃tion time(LCt50),the values of plasma cholinesterase(ChE)were checked at different time points after being exposed at different doses. RESULTS The mean concentrations of CPF aerosol at nine time points was 160.6 mg · m-3,the relative standard deviation value was 6.9%;the geometrical mean of aerosol particle size was 1.1 μm,and the geometric standard deviation was 1.8. The results met the technical requirements of Organization for Economic Cooperation and Development regarding acute inhalation exposure. Under these equipment conditions,the LCt50 of CPF acute inhalation of SD male rats was 1654.2 mg · m-3 · h,suggesting that plasma ChE inhibitory rate was higher with the increase in the exposing dose,and that there was a significant difference as compared with the controls(P<0.05). CONCLU⁃SION The model for whole-body dynamic-inhalation exposure of CPF is applicable to rats,which can serve as an experimental platform and technical support to inhalation vulnerability and the research on prevention and cure of organophosphate industrial products and nerve agents.