三聚氰胺急性毒性对临床合理用药的启示

Acute Toxicity of Melamine Implicates Rational Use of Medical Drugs

目的:从急性毒性分析三聚氰胺对有肾毒性药物的影响。方法:以昆明小鼠为对象,1次灌胃给药进行急性毒性试验,连续观察14d,记录小鼠中毒情况及死亡只数,Bliss法计算LD_(50)及95%可信限。对死亡及14d存活动物相关组织做病理观察。结果:小鼠灌胃给药LD_(50)与95%可信限为9899.97mg·kg^(-1)和7897.22～12410.63mg·kg^(-1);其中雌性为11375.00mg·kg^(-1)和7643.13～16929.01 mg·kg^(-1),雄性为8385.81mg·kg^(-1)和6334.49～11101.40mg·kg^(-1)。中毒动物肾远曲小管、集合管管腔有淡红色析出物及其钙化颗粒,伴上皮细胞变性坏死。结论:三聚氰胺终毒物可能为同系物的聚合体,临床用药应考虑三聚氰胺与有肾毒性药物的联合毒效应。

Objective： To analyze its toxic target organs and the rational use of clinic medical drugs from the acute toxicity of melamine in mice. Method： Mice were intragastrically administrated with melamine once and observed for 14 days. General state and dead ratio from its toxic effects were observed, the median lethal dose （ LD50 ） of melamine and its 95% confidence limits were calculated with Bliss＇s methods. Morphological changes of related organs were observed for determining the target organs. Result： LD50 and 95% confidence limits of melamine were 9899.97 mg·kg^-1 and 7897.22 mg·kg^-1 - 12410.63 mg·kg^-1, those in female were 11375.00 mg ·kg^-1 and 7643.13 mg·kg^-1- 16929.01 mg·kg^-1 , those in male were 8385.81 mg·kg^-1 and 6334.49 mg·kg^-1 - 11101.40 mg·kg^-1 respectively. The pathological changes included in degeneration and necrosis, were limited to the kidneys included in both of the sediments and the calcified particles within distal straight tubules and collecting ducts. Conclusion： The acute renal failure was resulted from the polymers derived from both of melamine and its derivations, the toxic joint actions of melamine with clinical drugs causing renal injury could be considered in clinic practices.