血清胸腺因子的大鼠围产期毒性试验研究

Study on perinatal toxicity of serum thymic factor in rats

目的:观察血清胸腺因子对大鼠妊娠晚期、分娩期、哺乳期及胚胎和胎仔出生后生长发育、学习能力以及生殖能力的影响。方法:选择交配后的雌性SD大鼠,每组20只,从妊娠第15天至哺乳期结束,分别按0.88、1.75和3.50 mg/kg连续皮下注射给予血清胸腺因子,同时设0.9%氯化钠注射液为溶剂对照组,定期称取F0代雌鼠体质量、摄食量;F1代仔鼠确定出生存活率、哺乳期存活率,生理发育、新生反射达标天龄,训练学习、记忆能力,观察出生第12周后的仔鼠交配后的生殖行为,测定胚胎毒性各项指标。结果:注射血清胸腺因子后,溶剂对照组和受试药物各剂量组F0代妊娠鼠和哺乳鼠各周的平均体质量增长和摄食量正常,仔鼠总量、性别比和出生存活率(96.3%~97.9%)和哺乳期存活率(97.7%~98.9%)基本一致;F1代仔鼠的哺乳期和离乳后仔鼠平均体质量增长和摄食量基本正常。溶剂对照组仔鼠的生理发育和新生反射时间点检查项目均为正常达标天龄,游泳适应时间(28.5±15.8)s,空间定位建立时间(134.9±44.1)s,暗室电击反射建立时间(4.9±3.1)s,建立记忆电击次数1.7±0.9;F1代性成熟大鼠溶剂对照组的同笼交配率100%,妊娠率90%,平均着床数10.6±2.1,平均活胎数10.2±1.9,死胎数3,畸形胎数1;以上指标受试药物各剂量组间未见明显变化,与溶剂对照组比较,差异均无统计学意义(P>0.05)。结论:在本实验条件下,溶剂对照组与血清胸腺因子3个剂量组的大鼠妊娠后期个体及F1代胚胎及胎仔出生后生长发育、神经行为以及生殖能力等均未发现明显异常,未见围产期毒性反应。

OBJECTIVE:To investigate effects of serum thymic factors on the growth and development,learning ability and reproductive ability of rats during the late pregnancy,delivery,lactation;as well as during postnatal periods of embryos and fetuses.METHODS:After successful mating,female SD rats were into 20 in each group.From the 15th day of pregnancy to the end of the lactation period,serum thymus factors were administered by continuous subcutaneous injection at 0.88,1.75 and 3.50 mg/kg respectively,and 0.9%chloride was provided.Sodium injection was the solvent control group.The body weight and food intake of the F0 generation female mice were regularly weighed;the birth survival rate and lactation survival rate of F1 generation offspring mice were determined,and the physiological development and neonatal reflexes reach the standard age,and the learning and memory abilities were trained.The reproductive behavior of the offspring after mating in the 12th week after birth was observed,and the various indicators of embryotoxicity was determined.RESULTS:After injection of serum thymic factors,the average body weight and food intake of the F0 generation pregnant and lactating mice in the solvent control group and the test drug groups were normal at each week,and the total number of offspring,sex ratio and birth survival rate(96.3%-97.9%)and the survival rate during lactation(97.7%-98.9%)were basically consistent.The average body weight and food intake of F1 generation mice during lactation and after weaning were basically normal.The physiological development and neonatal reflex time point examination items of the offspring in the solvent control group were all normal at the standard age,swimming adaptation time(28.5±15.8)s,spatial positioning establishment time(134.9±44.1)s,and darkroom electric shock reflex establishment time(4.9±3.1)s,the number of electric shocks to establish memory is 1.7±0.9;the cage mating rate of F1 generation sexually mature rats in the solvent control group was 100%,the pregnancy rate was 90%,the average number of implantations was 10.6±2.1,and the average number of live fetuses was 10.2±1.9,the number of stillbirths was 3,and the number of malformed fetuses was 1.The above indicators did not show significant changes in each dose group of the tested drug.Compared with the solvent control group,the differences were not statistically significant.CONCLUSION:Under the conditions of this experiment,no obvious abnormalities were found in the growth and development,neurobehavior,and reproductive ability of rats in late pregnancy and F1 generation embryos and fetuses in the three dose groups of the solvent control group and serum thymus factor,and no perinatal toxicity was found.