摘要
目的 研究雄黄对孕大鼠和孕兔胚胎/胎仔发育的影响，探讨雄黄的生殖毒性。方法 孕大鼠于妊娠第6~第15天ig给予雄黄125，250和550 mg·kg-1，每天1次，共10 d。阳性对照组孕大鼠于妊娠第10天im给予环磷酰胺10 mg·kg-1，正常对照组大鼠给予等容量的0.5%羧甲基纤维素钠，第20天处死解剖；孕兔于妊娠第6~18天ig给予雄黄31.3，62.5和125 mg·kg-1，阳性对照组孕兔从妊娠第6天~第18天ig给予沙利度胺200 mg·kg-1，每天1次，共13 d，第29天处死解剖。观察给药前后临床表现和毒性症状，处死后称体质量及各雄黄组子宫、胎仔和胎盘总质量，观察并记录胎仔外观、着床数和活胎数，测量胎仔顶臀长和尾长，并计算晚期胚胎流失率。胎仔用茜素红染色观察骨骼，用Bouin液固定检查内脏。结果孕大鼠雄黄125，250和550 mg·kg-1组没有明显的母体毒性反应；与正常对照组比较，雄黄550 mg·kg-1组胎仔体质量、尾长和顶臀长有显著差异（P〈0.05），子宫连胎质量、子宫净质量、胎仔总质量、胎盘总质量、平均胎仔数、活胎率和晚期胚胎流失率等无显著差异；胎仔外观、骨骼和内脏均未见畸形。孕兔雄黄62.5和125 mg·kg-1表现明显临床毒性反应，孕兔31.3，62.5和125 mg·kg-1组子宫连胎质量、子宫净质量、胎仔总质量、胎盘总质量、活胎率、胎仔体质量、尾长和顶臀长均随着雄黄剂量的增加而降低，晚期胚胎流失率随着雄黄剂量的增加而上升，其中雄黄125和62.5 mg·kg-1组活胎率分别为45.76%和72.73%，与正常对照组活胎率（90.90%）比较，有显著差异（P〈0.01）。但在兔胎仔的外观、骨骼和内脏检查中未发现有畸形。结论 兔比大鼠对雄黄的毒性更敏感，表现为母体的毒性反应、活胎率下降和晚期胚胎流失率上升。未发现雄黄对大鼠和兔有致畸作用。
OBJECTIVE To investigate the effects of realgar on the embryo-fetal development in pregnant rats and rabbits, and explore its reproductive toxicity. METHODS Pregnant rats were ig given realgar 125, 250 and 550 mg·kg-1 from the 6th to 15th day after pregnancy, once daily, for 10 d. Rats in positive control groups were im injected cyclophosphamide 10 mg·kg-1, rats in normal control group were given 0.5%CMC-Na, and the pregnant rats were sacrificed on the 20th day. The pregnant rabbits were ig given realgar 31.3, 62.5 and 125 mg·kg-1 on the 6th to 18th day after pregnancy, rats in positive control groups were ig given thalidomide 200 mg·kg-1, once daily, for 13 d. And the pregnant rabbits were sacrificed on the 29th day. The clinical manifestation and toxical symptoms were observed before and after administration. Mass of uteruses, fetuses and placentas of each dose group were measured after sacrificed. Appearance of fetuses was examined, lengths of rown-rump and tail were measured, and the number of implantation and living fetuses was countered. Fetal skeletons were examined by alizarin red staining and fetuses were fixed by Bouin solution to examine the fetal viscera. RESULTS No apparent toxic reaction in pregnant rats was showed in realgar groups. Among the indexes of embryo-fetus development, compared with negative control group, apart from realgar 550 mg·kg-1 group, no significant difference was found in mass of uterus-fetuses, uterus, fetuses, and placentas, and the average numbers of fetus, the living fetus rate and late fetus losing rate in realgar 250 and 125 mg·kg-1 groups. However, there was significant difference in realgar 550 mg·kg-1 group（P〈0.05）; no malformations were found in rat fetus appearances, skeleton, and viscera. While in pregnant rabbits, an obvious clinical toxic reaction was found in realgar 125 and 62.5 mg·kg-1 groups, the indexes of uterus-fetuses mass, uterus, fetuses, and placentas, and the average numbers of fetus, the living fetus rate signifinantly decreased, while th
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2013年第6期1007-1013,共7页
Chinese Journal of Pharmacology and Toxicology
基金
国家科技重大专项(2009ZX09502-002)~~
关键词
雄黄
胚胎
生殖毒性
毒性作用
realgar
embryo
proconception injuries
toxic actions
