来曲唑对SD大鼠促排卵及致畸作用的研究

目的:评价来曲唑对SD大鼠促排卵作用及其对胎鼠可能的致畸影响。方法:58只清洁级SD雌性大鼠随机分为空白对照组、溶剂(CMC)对照组及来曲唑不同剂量组(0.26mg/kg、0.52mg/kg、0.78mg/kg),分别于动情前期灌胃相应试剂,次晚合笼,阴栓及阴道涂片阳性者为孕0d,观察孕鼠的摄食饮水等一般情况,定期测体质量,于孕20d剖腹取胎仔,记录黄体数、着床腺数、吸收胎数、活胎数、死胎数、胎鼠体质量、身长、尾长等参数;每孕鼠取一半存活胎鼠进行内脏形态学检查,另一半做骨骼形态学检查。结果:CMC对试验结果无影响。来曲唑各试验组均对大鼠有促排卵作用,但可引起部分孕鼠流产,其活胎数、着床腺数低于对照组;胎鼠的植入前和植入后死亡率均高于对照组;来曲唑0.26mg/kg、0.52mg/kg对胎鼠无致畸作用,来曲唑0.78mg/kg组胎鼠内脏畸形率高于对照组。结论:来曲唑可促进大鼠的卵泡发育,但增加胎鼠的植入前和植入后死亡率;在≥0.78mg/kg剂量时,可能增加胎鼠的内脏畸形率。

Study of Letrozole's Ovulation Induction and Teratogenicity in SD Rats

Objective： To evaluate the effects of letrozole on ovulation induction and teratogenicity in SD rats. Method： Fifty-eight SD female rats were randomly divided into negative control group （NS）, solvent control group （CMC） and three letrozole （0.26 mg/kg, 0.52 mg/kg, 0.78 mg/kg） groups. The rats were administered with corresponding reagents on proestrus and were placed together with SD male rats next night. Detection of sperm in the vaginal smear （taken as evidence of mating） at the end of the dark cycle （8 ： 00 am） served to designate gestation day 0. The pregnant rats received cesarean section on the day 20 after pregnancy. The corepus luteum, plant gland, absorbed fetus, live fetus, dead fetus, body weight and body length were measured. The fetuses from each uterus were selected alternately either for skeletal examination or for visceral examination. Results： CMC didn＇t affect the results of experiment. Letrozole induce ovulation in rats, but it lead to abortion in some cases. The live fetus, plant glands in letrozole groups were fewer than those in control groups. The pre-plant dead rate and 15ost-plant dead rate in letrozoie groups were higher than those in control groups. Letrozole had no teratogenic effect in fetuses at the dose of 0.26 mg/kg, 0.52 mg/kg, but at the dose of 0.78 mg/kg it caused visceral teratogenicity in some of live fetuses. Conclusion： Letrozole could induce ovulation in rats but increase the pre-implantation loss and post-implantation loss of fetuses. It may increase the visceral teratogenicity ratio of fetuses at the dose of 0.78 mg/ kg.