注射用重组人B淋巴细胞刺激因子受体-抗体融合蛋白对大鼠生育力及早期胚胎发育的毒性作用

Toxic Effect of Recombinant Human B Lymphocyte Stimulating Factor Receptor-Antibody Fusion Protein for Injection on Fertility and Early Embryonic Development of Rats

目的观察注射用重组人B淋巴细胞刺激因子受体-抗体融合蛋白(RCT-18)对大鼠生育力及早期胚胎发育的毒性作用。方法将SD大鼠随机分为4组,分别经皮下注射RCT-18 129、37、11 mg/(kg.d)和0.9%NaCl注射液,每2 d给药1次。雄鼠连续给药5周、雌鼠连续给药2周后,按雌雄1∶1的比例合笼交配,合笼期为2周,计算交配率。雄鼠继续给药至交配成功,雌鼠继续给药至妊娠第6天。实验过程中观察动物的一般反应、体重及摄食量变化。确定雌鼠受精后处死雄鼠,解剖检查睾丸和附睾等生殖器官。于妊娠第15天解剖孕鼠,综合评价妊娠及胚胎形成和早期发育等情况。结果 RCT-18高、中、低剂量组雌性和雄性大鼠均未出现明显的母体毒性反应。各组大鼠各脏器均未见肉眼可见的异常。各剂量RCT-18对大鼠的交配率、妊娠率、生殖系统脏器重量和系数以及早期胚胎发育均无明显影响。结论RCT-18对SD大鼠的生育力及早期胚胎发育无明显毒性作用。

Objective To observe the toxic effect of recombinant human B lymphocyte stimulating factor receptor-antibody fusion protein RCT-18 for injection on fertility and early embryonic development of rats. Methods SD rats were randomly divided into one control and three test groups. The rats in three test groups were injected s.c. with RCT-18 once 2 days at dosages of 129, 37 and 11 mg/（kg＇d） respectively, while those in control group with 0. 9% NaC1. Male rats were administered for 5 weeks, while female ones for 2 weeks prior to cohabitation at a ratio of I ： 1 for 2 weeks. The mating rate was calculated. Male rats were further administered until a successful mating, while female rats until the clay 6 after pregnancy. The general reaction, bodyweight and food consumption were observed. After the pregnancy of female rats was confirmed, male rats were anatomized and observed for reproductive organs such as testis and epididymis. The pregnant female rats were anatomized on day 15 after pregnancy, based on which the pregnancy, embryogenesis and early embryonic development were evaluated comprehensively. Results No obvious maternal toxicities or visual abnormalities of organs were observed in male or female rats in three test groups. The RCT-18 at various dosages showed no significant effect on mating rate, pregnancy rate, the weight and coefficient of reproductive organ as well as early embryonic development of rats. Conclusion RCT-18 showed no obvious toxic effect on the fertility and early embryonic development of SD rats.