模拟一次快速静脉注射和静脉滴注体外染毒模型的构建  

Construction of in vitro administration models that simulate one-time rapid intravenous injection and intravenous infusion

作　　者：付大维 闫赖赖[2] 陈洁 付娟玲[1] 姚碧云[1] 赵鹏[1] 郝卫东[1] FU Da-wei;YAN Lai-lai;CHEN Jie;FU Juan-ling;YAO Bi-yun;ZHAO Peng;HAO Wei-dong(Department of Toxicology,School of Public Health,Peking University,Beijing 100191,China;Department of Laboratonal Science and Technology,School of Public Health,Peking University,Beijing 100191,China)

机构地区：[1]北京大学公共卫生学院毒理学系,食品安全毒理学研究与评价北京市重点实验室,北京100191 [2]北京大学公共卫生学院卫生检验学系,北京100191

出　　处：《毒理学杂志》2021年第2期104-109,共6页Journal of Toxicology

基　　金：科技部-国家重点研发计划(2017YFC1600203);国家自然科学基金(81370079,81001253)。

摘　　要：目的以硝酸镧La(NO_(3))_(3)为受试物,构建模拟一次快速静脉注射和静脉滴注2种体外染毒模型。方法自主设计由储液室、染毒室和废液室组成的染毒装置,由蠕动泵软管连接各室以实现液体单向和定速传输。根据预设的毒代动力学参数,构建模拟一次快速静脉注射和静脉滴注的体外染毒模型。以电感耦合等离子体质谱仪(ICP-MS)测定不同时间点染毒室中La(NO_(3))_(3)含量。利用PKsolver和GraphPad Prism 7软件对La(NO_(3))_(3)浓度-时间曲线进行分析,通过比较毒代动力学参数实测值和理论值对2种染毒模型进行评估。结果2种体外染毒模型的消除速率常数、半衰期、清除率和曲线下面积等参数实测值均与理论值接近,拟合系数R^(2)均>0.9900。结论由蠕动泵连接储液室、染毒室和废液室组成的染毒装置可体外模拟一次快速静脉注射和静脉滴注2种染毒模型。本研究为优化体外毒性测试染毒方法提供了初步实验依据,对基于体外毒性测试的化学品风险评估具有一定理论和实际意义。Objective Selecting La(NO_(3))_(3)as a test chemical,to construct in vitro administration models simulating one-time rapid intravenous injection and intravenous infusion,respectively.Methods One kind of administration device including liquid storage compartment,administration compartment and waste compartment,was self-designed to construct in vitro administration models that simulate one-time rapid intravenous injection and intravenous infusion,respectively.Peristaltic pump was used to connect each compartment and realize unidirectional and constant speed transmission of liquid.ICP-MS was used to detect the content of La(NO_(3))_(3)in the administration compartment liquid at different time points.PKsolver and GraphPad Prism 7 were used to analyze the concentration-time curves.The in vitro administration models were evaluated by comparing the measured and theoretical values of toxicokinetic parameters.Results In the two in vitro administration models about La(NO_(3))_(3),the measured values of elimination rate constant,half-life,clearance rate and area under the curve were very close to the theoretical values,and the fitting coefficient R^(2)was greater than 0.9900.Conclusion The self-designed administration device can be used to construct in vitro administration models that simulate one-time rapid intravenous injection and intravenous infusion,respectively.This study provide preliminary experimental bases for optimizing the administration method of in vitro toxicity testing,and have certain theoretical and practical significance for the risk assessment of chemicals based on in vitro toxicity testing.

关 键 词：体外染毒模型 一次快速静脉注射 静脉滴注 毒代动力学 硝酸镧 

分 类 号：R99[医药卫生—毒理学] R114[医药卫生—药学]