TQ17对大鼠胚胎-胎仔发育毒性研究

Study on the Toxicity of TQ17 to Rat Embryo-Fetal Development

目的通过在大鼠致畸敏感期给药,观察非甾体炎抗炎药TQ17是否有母体毒性和胚胎-胎仔发育毒性。方法SD大鼠,120只雌鼠,90只雄鼠,90只交配成功的雌鼠随机分为4个组,分别为TQ17大、小剂量组(30,350 mg·kg-1·d-1),环磷酰胺组(环磷酰胺15 mg·kg-1·d-1)和模型对照组(0.5%羧甲基纤维素钠溶液)。TQ17小、大剂量组和模型对照组于妊娠第6天至第15天灌胃给药,环磷酰胺组于妊娠第12天皮下注射给药。实验中观察孕鼠饮水、摄食、生长等一般状况,每周称大鼠体质量。妊娠第20天解剖孕鼠,记录黄体数、连胎子宫质量、着床数、死胎数、活胎数、胎仔性别、顶臀长、尾长及体质量,观察活胎外观异常。每窝1/2胎仔作骨骼畸形检查,另1/2胎仔作内脏检查。结果与模型对照组比较,TQ17大剂量组孕鼠妊娠第7天至第15天体质量极显著降低,胎鼠的胸骨畸形或变异显著增加。在该实验条件下,TQ1730 mg·kg-1·d-1对母体一般状况和子代发育没有影响,350 mg·kg-1·d-1对胎鼠胸骨发育有毒性作用。结论TQ17对大鼠胚胎胎仔发育有致畸风险。

Objective To observe the maternal and embryo-fetal development toxicity of TQ17 in pregnant rats after the drug administration in the teratogenic sensitive period.Methods SD rats including 120 females,90 males,and 90 successfully mated females were randomly divided into 4 groups:TQ17 low dose and high dose groups(30,350 mg·kg-1·d-1),cyclophosphamide group(cyclophosphamide 15 mg·kg-1·d-1)and model control group(0.5%sodium carboxymethylcellulose solution,0.5%CMC-Na).These rats were orally administered by gavage with TQ17 or 0.5%CMC-Na in low and high dose groups and model control groups from the 6th day to the 15th day of pregnancy.The cyclophosphamide group was injected subcutaneously with cyclophosphamide on the 12th day of pregnancy.The general conditions of the pregnant rats,such as growth,food,and water intake were recorded,and the rats were weighed weekly.The rats were sacrificed on the 20th day of pregnancy,and the number of corpus luteums,the uterus,the number of implantation,dead or live fetus,the sex,the length of top buttock and tail,and the body weight were recorded.The appearance of live fetus was identified for abnormality.Half fetuses in each litter were examined for skeletal deformity and the other half was used for viscera check.Results Compared with the model control group,the body weight of rats in TQ17 high dose group decreased significantly.At the same time,the cases of sternal malformation or variation increased significantly in fetal rats.Under the conditions of this experiment,TQ17 at the dose of 30 mg·kg-1·d-1 had no effect on the general condition of the mother and the growth of the offspring,while the dose of 350 mg·kg-1·d-1 had toxic effect on the development of the fetal sternum.Thus.Conclusion TQ17 have the risk of teratogenicity on rat embryo-fetal development.