三聚氰胺等物质给予幼年恒河猴的毒性试验  

Chronic Toxicity Study of Melamine and Cyanuric Acid on Juvenile Rhesus Monkeys

作　　者：高虹[1] 何君[1] 贺晓玉[1] 马耀文[1] 孙井江[1] 李洋[1] 高洁[1] 秦川[1] 

机构地区：[1]中国医学科学院,北京协和医学院,医学实验动物研究所,卫生部人类疾病比较医学重点实验室,国家中医药管理局人类疾病动物模型三级实验室,北京100021

出　　处：《中国比较医学杂志》2012年第6期1-4,8,共5页Chinese Journal of Comparative Medicine

摘　　要：目的观察三聚氰胺及其同系物给予动物后,导致肾脏损伤、形成结石的过程,及肾脏损伤的恢复过程。方法选择6月龄恒河猴6只,雌雄各半,随机分为3组,2只/组,分别为T1(140 mg/kg三聚氰胺和14 mg/kg三聚氰酸),T2(140 mg/kg三聚氰胺和50mg/kg腺嘌呤)和T3组(140mg/kg三聚氰胺)。连续70 d口服受试物,观察动物的一般状态,分别于不同时间点进行血液学、血生化、尿常规和肾脏B超的检测;并连续观察18个月,观察动物的生长发育情况。结果 1.各剂量组动物在给予受试物8周后所有动物肾脏中均出现多个结石;停止给予受试物后,所有动物结石数量和大小均呈下降趋势,至停止给予受试物16个月后,全部动物肾脏均未检测出结石。2.各剂量组,血清中β2微球蛋白(β2-MG)和尿酸(UA)等指标随着给药时间的延长而有所增高,但在正常范围内。在动物的恢复期,此两项指标的数值明显下降。结论 1.单纯三聚氰胺(相当于人体使用量48 mg/kg.w.d)不能造成恒河猴肾脏功能的明显损害,可形成肾结石。2.在三聚氰酸或腺嘌呤存在的情况下,三聚氰胺可以造成恒河猴肾功能指标β2-MG和UA在正常范围内升高,并可在肾脏形成结石;。3.经过16个月的恢复所有动物结石无法检出,其中三聚氰胺组动物恢复最快。Objective To observe the symptoms of juvenile Rhesus monkey taking orally melamine and melamine analog.Symptoms including： kidney damage,kidney stone,process of kidney damage reversibility.Methods 6month old rhesus monkeys were chosen,half male and half female,randomly divided into 3 groups,each group has 2 monkeys.group T1（melamine,140 mg/kg;cyanuric acid,14 mg/kg）,group T2（melamine,140 mg/kg;adenine,50 mg/kg）,and group T3（melamine,140 mg/kg）.Each group was given its own dose for 10 weeks.Then the animal＇s daily condition was observed,and their CBC,blood chemistry,urine routine and B scan were tested at different time point.The animals were kept for 18 months;their growth and development condition were observed.Results 1.At each group,lots of stones was found on the kidney after administering drug for 8 weeks.After stopping administration,all stones became smaller and less,and no stone could be tested till stopping test articles for 16 months.2.At each group,β2-MG and UA in blood serum was increased after administration,but all of them fluctuated in normal limit;and in reversibility,β2-MG and UA were lower than before.Conclusions 1.melamine（48mg/kg.w.d as in human body） could not cause Rhesus monkey kidney damage,but can cause kidney stone.2.When cyanuric acid and adenine existed,melamine could increased β2-MG and UA in normal range and also could cause kidney stone.3.The stone of all animals couldn＇t be detected for 16 months,the animals of oral melamine recovered faster.

关 键 词：三聚氰胺 三聚氰酸 腺嘌呤 恒河猴 肾结石 

分 类 号：R332[医药卫生—人体生理学]