亚硒酸钠在雏鸭血液和组织中的毒物代谢动力学研究

Study on the blood and tissue toxicokinetics of sodium selenite in ducklings

【目的】研究中毒量亚硒酸钠在雏鸭血液和组织中的毒物代谢动力学,为临床上科学合理地用其预防雏鸭硒缺乏病和硒中毒病提供参考依据。【方法】以1日龄健康蛋用金定雏鸭100只(公母各半)为试验动物,饲喂20 d后口服中毒量亚硒酸钠(1 g/L),用2,3-二氨基萘荧光法,测定雏鸭口服中毒量亚硒酸钠后不同时间血液和组织中的硒含量,通过MCPKP软件计算中毒量亚硒酸钠在雏鸭血液和组织中的毒物代谢动力学参数。【结果】中毒量亚硒酸钠在雏鸭血液中的毒物代谢动力学特征符合一级吸收二室开放模型,其主要动力学参数为:吸收半衰期(t1/2Ka)为0.624 h,达峰时间(Tmax)为2.399 h,消除半衰期(t1/2β)为138.241 h,曲线下面积(AUC)为10.694 mg/(L.h),总表观分布容积(Vd)为22.398 L/kg。中毒量亚硒酸钠在雏鸭肝脏、肾脏、脾脏、肌胃中的毒物代谢动力学特征均符合一级吸收二室开放模型,吸收半衰期(t1/2Ka)分别为0.297,1.520,5.181,4.599 h,达峰时间(Tmax)分别为2.186,9.362,22.045,20.082 h,消除半衰期(t1/2β)分别为914.988,149.994,179.025,166.294 h;胰脏的毒物代谢动力学特征符合滞后一级吸收二室开放模型,吸收半衰期(t1/2Ka)为6.579 h,达峰时间(Tmax)为21.480 h,消除半衰期(t1/2β)为71.519 h;肌肉的毒物代谢动力学特征符合滞后一级吸收一室开放模型,吸收半衰期(t1/2Ka)为20.700 h,达峰时间(Tmax)为30.164 h,消除半衰期(t1/2β)为20.587 h;心脏的毒物代谢动力学特征符合一级吸收一室开放模型,吸收半衰期(t1/2Ka)为1.159 h,达峰时间(Tmax)为8.147 h,消除半衰期(t1/2β)为145.331 h。【结论】与亚硒酸钠药物代谢动力学特征相比,雏鸭口服中毒量亚硒酸钠后,硒的吸收、分布均比较迅速,消除缓慢。

[Objective] The experiment characterized the blood and tissue toxicokinetics of Sodium Selenite with a toxic dose in ducklings. [Method] The selenium content in blood and tissues of ducklings feeding Sodium Selenite with a toxic dose at different times were determined by 2,3-diamine naphthalene fluorescence method,and then the toxicokineties parameters calculated by MCPKP soft. [Result] The characteristics of blood toxicokineties were consistent with the first order absorption and two compartment open models. The primary kinetics parameters：the absorption half life（t1/2Ka）was 0. 624 h; the time of reaching maximum concentration（Tmax） 2. 399 h, the half-life of elimination （t1/2β） 138. 241 h, the area under the curve（AUC） 10. 694 mg/（L · h）,and the volume of distribution（Vd） 22. 398 L/kg. The characteristics of liver,kidney,spleen and muscular stomach toxicokinetics conformed with the two compartment open models with first order absorption. The absorption half life（t1/2Ka）was 0. 297,1. 520,5. 181 and 4. 599 h respectively,and the time of reaching maximum concentration（Tmax） 2. 186,9. 362,22. 045 and 20. 082 h respectively,and the half-life of elimination（t1/2β）914. 988,149. 994,179. 025 and 166. 294 h repectively. The pancreas toxicokinetics of Sodium Selenite was found to be in agreement with the two compartment open models and first order absorption with a lagtime. The absorption half life（t1/2Ka）Was 6. 579 h,the time of reaching maximum concentration（Tmax） 21. 479 h;and the half-life of elimination（t1/2β） 71. 519 h. The muscle toxicokinetics of Sodium Selenite was described by the one compartment open model and first order absorption with a lagtime. The absorption half life（t1/2Ka）Was 20. 700 h,the time of reaching maximum concentration（Tmax） 30. 164 h,and the half-life of elimination（t1/2β） 20. 587 h. The heart toxicokinetics of Sodium Selenite found to be in agreement with the one compartment open model with first order absorption. The absorption half life（t1/2Ka） was 1. 159 h ; the time of reaching maximum concentration（Tmax） 8. 147 h, and the half-life of elimination（t1/2β） 145. 331 h. [Conclusion] A toxic oral dose of Sodium Selenite was rapidly absorbed and distributed in ducklings, but eliminated slowly.