滋肾育胎丸对SD大鼠胚胎-胎仔发育的影响

Effect of Chinese traditional medicine Zishen Yutai pills on embryo-fetal development of SD rats

目的:观察滋肾育胎丸对SD大鼠胚胎-胎仔发育的影响,为临床用药提供参考。方法:在着床至硬腭闭合期间(GD6~15)灌胃(ig)给予SD妊娠大鼠不同剂量(6,12和24 g·kg^(-1))的滋肾育胎丸,溶媒对照组和阳性对照组动物分别给予纯化水和环磷酰胺。其中,阳性对照组于GD12皮下注射环磷酰胺(15mg·kg^(-1))。检测并记录母鼠体重、摄食量、胚胎着床、胎仔吸收、雌二醇(E2)、孕酮(P)和睾酮(T)激素,检测胎仔生长发育和畸形等情况。结果:滋肾育胎丸对孕鼠的妊娠结局(平均黄体数、平均着床数、平均活胎数、活胎率、吸收胎率和死胎率等)、对胎仔的外观、内脏和体格生长发育(窝均体重、身长、尾长和胎盘重)均未见明显影响;滋肾育胎丸各剂量组睾酮、孕酮和雌二醇水平均在正常范围内波动。结论:滋肾育胎丸对SD大鼠胚胎-胎仔发育毒性的未见不良反应水平(NOAEL)为12 g·kg^(-1),是大鼠等效剂量的8倍,临床人用剂量的48倍。剂量达24 g·kg^(-1)时可使母鼠宫外增重减少。

Objective：To investigate the potential reproductive toxicity of Zishen Yutai pills on embryo-fetal development in SD rats,and provide reference for clinical medication. Methods：Various doses（6,12 and 24g·kg^-1） of Zishen Yutai pills were given to SD pregnant rats by intragastric administration for the period from implantation to hard palate closure. Distilled water and cyclophosphamide were used as solvent control and positive control,respectively. The rats in the positive control group were intraperitoneally injected with cyclophosphamide at a dose of 15 mg·kg^-1on GD12. The effects on maternal weight loss,food intake,implantation and fetal resorption as well as the effects on fetal physical growth and congenital malformations were recorded. Results：Zishen Yutai pills had no toxicities on the pregnancy outcome of pregnant rats（the average numbers of corpus luteum,implantation,and live births,live births rate,absorption rate and stillbirth rate,etc.） and the appearance of the foetus,visceral,and physical growth and development（body weight,body length,tail length and placental weight）. The testosterone,progesterone and estradiol levels fluctuated within the normal range in all the groups. Conclusion：The no observed adverse effect level（NOAEL） of Zishen Yutai pills for embryo-fetal development in rats is 12 g·kg^-1,which is 8times of the equivalent rat dose and 48 times of equivalent clinical dose. Maternal toxicity as decreasing extrauterine weight gain was observed at the dose of 24 g·kg^-1.