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目的探讨重组戊型肝炎疫苗对大鼠的生殖毒性。方法将Wistar雌性大鼠分为4组:低剂量组(每只20μg HEV)、高剂量组(每只40μg HEV)、生理盐水对照组及佐剂对照组,每组30只。雌鼠于交配前给药2次,初次给药后2周进行2次给药,2次给药后1周,进行雌雄鼠合笼交配,于妊娠7和14 d进行3、4次给药。每天观察雌鼠一般临床症状;交配前每周称雌鼠体重1次,交配后每周称体重2次,每周定期测定1次摄食量;于妊娠21 d安乐死孕鼠,分离出胎仔,检测疫苗对雌鼠生殖能力、胎仔发育、胎仔骨化程度、胎仔内脏畸形的影响,取孕鼠和胎仔血液,分离血清,ELISA法检测抗HEV Ig G抗体水平。结果各组大鼠精神状态未见异常,皮毛光亮,灵敏,大小便色正成形,注射局部未见充血、肿胀、溃烂、硬结等;疫苗对孕鼠体重、摄食量均无明显影响(P<0.05);各剂量组窝平均着床数、窝平均黄体数、窝平均活胎数、受孕率、活胎率、吸收胎率、死胎率、畸胎率与生理盐水对照组和佐剂对照组相比,差异均无统计学意义(P>0.05);各剂量组胎仔身长、尾长、体重、胎盘重和性别比与生理盐水对照组和佐剂对照组相比,差异均无统计学意义(P>0.05);各剂量组胎仔上枕骨的骨化程度均在0级和Ⅰ级正常范围以内,胸骨骨化不全率与生理盐水及佐剂对照组相比,差异无统计学意义(P>0.05);各组胎仔内脏均未见畸形;孕鼠及胎仔血清中均检测到抗HEV Ig G抗体。结论重组戊型肝炎疫苗对孕鼠及胎仔安全、有效。
Objective To investigate the reproductive toxicity of recombinant hepatitis E vaccine in rats. Methods Wistar female rats were divided into 4 groups: low dose group (20μg HEV each), high dose group (40μg HEV each), normal saline control group and adjuvant control group, 30 rats in each group. Females were administered 2 times before mating, 2 weeks after the first administration, and 1 week after the second administration. The male and female rats were intercoupled with cages, and were administered 3 and 4 doses on days 7 and 14 of gestation . Female rats were observed daily clinical symptoms; before mating, weighed 1 female body weight, weighed weekly weekly weighed 2 times a week to determine the amount of food intake; pregnant 21 d pregnant eutapepticems fetus, test The effects of the vaccine on reproductive abilities, fetal development, fetal ossification and fetal visceral malformation of the female mice were measured. The serum of pregnant mice and fetus was separated and the serum was separated. The antibody against HEV Ig G was detected by ELISA. Results There was no abnormal mental state in the rats in each group. The fur was bright and sensitive. The urine and urine were forming. There was no hyperemia, swelling, ulceration and induration in the injected part. The vaccine had no significant effect on body weight and food consumption (P < 0.05). The average number of implantation, average number of livers in litter, average live litter size, pregnancy rate, live fetus rate, absorbed fetus rate, stillbirth rate and teratogenic rate in each dose group were similar to those in control group and adjuvant control group (P> 0.05). There was no significant difference in body length, tail length, body weight, placental weight and sex ratio between saline group and adjuvant control group in each dose group (P> 0.05) > 0.05). The ossification degree of the occipital bone in each dose group was within 0 grade and within the normal range of grade Ⅰ, there was no significant difference in the rate of sarcoplasmic stenosis between normal saline and adjuvant control group (P> 0.05 ). No abnormalities were observed in the viscera of all fetuses. Anti-HEV Ig G antibodies were detected in the serum of pregnant rats and fetuses. Conclusion Recombinant hepatitis E vaccine is safe and effective for pregnant rats and fetuses.