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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 study the effects of realgar on the embryo / fetal embryo development in pregnant rats and pregnant rabbits and to explore the reproductive toxicity of realgar. Methods Pregnant rats were given realgar with 125, 550 and 550 mg · kg-1 of realgar on the 6th to the 15th day of gestation, once a day for 10 days. Rats in the positive control group were given cyclophosphamide 10 mg · kg-1 on the 10th day of gestation while rats in the normal control group were given 0.5% sodium carboxymethylcellulose at the same volume. The rats were sacrificed on the 20th day. Pregnant rabbits Pregnancy 6 to 18 days ig given realgar 31.3,62.5 and 125 mg · kg-1, the positive control group of pregnant rabbits from 6th to 18th day of pregnancy ig given thalidomide 200 mg · kg-1, 1 day , A total of 13 days, the first 29 days of anatomy. The clinical manifestations and toxic symptoms were observed before and after treatment. The body weight and the total mass of uterus, fetus and placenta of each realgar were measured after sacrifice. The appearance, implantation number and number of live fetuses were observed and recorded. And calculate the late embryo loss rate. Fetal alizarin red stained bone observation, with Bouin fluid fixed visceral examination. Results There was no significant maternal toxicity in realgar at 125, 550 and 550 mg · kg -1 groups. Compared with the normal control group, the body weight, tail length and top-buttock length of 550 mg · kg-1 group were significantly different (P <0.05). There was no significant difference in uterine mass, uterine mass, total mass of fetal uterus, total mass of placenta, mean litter size, live fetus rate and late embryo loss rate. Pregnancy rabbit realgar at 62.5 and 125 mg · kg-1 showed significant clinical toxicity. The pregnant women with 31.3,62.5 and 125 mg · kg-1 groups had the same quality of uterine tubal mass, uterine mass, total fetal weight, total placenta mass, , Body mass, tail length and top rump length all decreased with the increase of realgar dosage, and the rate of late embryo loss increased with the increase of realgar dosage. The live birth rates of realgar at 125 and 62.5 mg · kg -1 were 45.76% and 72.73%, respectively, which were significantly different from those of the control group (90.90%) (P <0.01). However, in the appearance of fetal fetus, bone and visceral examination found no deformity. Conclusions Rabbits are more sensitive to the toxicity of realgar than the rats, showing maternal toxicity, decreased live birth rate and increased late embryo loss rate. Realgar has not been found to cause teratogenic effects on rats and rabbits.