注射用重组人B淋巴细胞刺激因子受体-抗体融合蛋白对家兔胚胎及胎仔发育的毒性作用

Toxic Effect of Recombinant Human B Lymphocyte Stimulating Factor Antagonist-Antibody Fusion Protein for Injection on Embryo-fetal Development of Rabbits

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)对家兔胚胎及胎仔发育的毒性作用。方法将受精后的雌兔随机分为RCT-18高、中、低剂量组和阴性对照组,每组15只,于妊娠第6～18天分别经皮下注射RCT-18 51.3、14.7、4.4 mg/(kg.d)和0.9%NaCl注射液,每2 d注射1次,共7次。实验过程中每天观察动物的一般反应、体重及摄食量变化,于妊娠第28天解剖孕兔,对着床、吸收胎、死胎、活胎、黄体进行计数,对胎仔的体重、身长、尾长以及外观形态、内脏和骨骼发育等指标进行考察。结果各组孕兔、胚胎形成、胎仔生长发育、外观形态、内脏和骨骼发育等各项指标均无明显异常,与阴性对照组比较,多数指标差异无统计学意义(P>0.05)。结论 RCT-18对妊娠家兔未见明显母体毒性和胚胎-胎仔发育毒性,无致畸作用。

Objective To observe the toxic effect of recombinant human B lymphocyte stimulating factor antagonist-antibody fusion protein RCT-18 on embryo-fetal development of rabbits.Methods Female rabbits after fertilization were randomly divided into three test and one control groups,15 for each.The rabbits in three test groups were injected s.c.with RCT-18 at dosages of 51.3,14.7 and 4.4 mg /（kg·d） respectively on days 6 ～ 18 after pregnancy,while those in control group with 0.9% sodium chloride,once 2 days for 7 times.The rabbits were observed for general reaction,bodyweight and feed consumption every day,then autopsied on day 28 after pregnancy and counted for implantation,resorption,dead and live fetuses as well as corpus luteum,of which the fetuses were evaluated for bodyweight,body length,tail length,gross external as well as visceral and skeletal alterations.Results The pregnant female rabbits,embryo-fetal development as well as the gross external,visceral and skeletal alterations of fetuses in the three test groups showed no abnormalities,most of which showed no significant difference with those in control group（P 0.05）.Conclusion RCT-18 showed no obvious maternal or embryo-fetal toxicity or teratogenicity in rabbits.