中药朱砂对小鼠显性致死突变性研究

Study on dominant lethal mutagenicity of cinnabar in mice

目的采用啮齿类动物显性致死试验,初步研究中药朱砂对小鼠受孕及胚胎死亡的影响,探讨其潜在的生殖细胞遗传毒性。方法分别以0.08、0.25和0.80 g/kg·bw朱砂经口灌胃雄性小鼠5 d,再与雌性小鼠交配,重复进行5批,覆盖整个生精周期以研究朱砂对不同发育阶段的生殖细胞的影响。各批次分别于同笼后第17 d,处死雌性小鼠检查子宫内容物,观察记录雌鼠受孕数、胚胎着床数、活胚胎数和死亡胚胎数等指标。结果0.80 g/kg·bw朱砂剂量组、阳性对照组第1~2周交配的孕鼠平均死胎数增加,阳性对照组第1~3周交配的孕鼠平均活胎数降低,与阴性对照组比,差异具有统计学意义(F=7.39,F=13.15,F=3.63,F=5.99,F=1.16,P<0.05);0.80 g/kg·bw朱砂剂量组第1~2周、阳性对照组第1~3周交配小鼠的有死胎孕鼠率、胚胎死亡率升高,与阴性对照组比,差异具有统计学意义(χ^(2)=7.46,χ^(2)=12.23,χ^(2)=17.46,χ^(2)=29.00,χ^(2)=4.69,F=8.38,F=15.48,F=1.30,P<0.05);0.80 g/kg·bw朱砂剂量组第2周、阳性对照组第1~3周交配的小鼠着床前后诱发显性致死率升高;朱砂各剂量组各批次小鼠受孕率与阴性对照组比差异无统计学意义(χ^(2)=0.03~1.03,P>0.05)。结论在本实验条件下,朱砂剂量组出现显性致死指标异常,提示朱砂可能具有致突变作用,朱砂对小鼠生殖细胞遗传毒性的LOAEL为0.80 g/kg·bw。

Objective In order to evaluate the genetic toxicity of cinnabar,the mice dominant lethal test was conducted.Methods Male mice were gavaged for 5 consecutive days with 0.08,0.25,0.80 g/kg·bw cinnabar,with positive and negative controls.Then individual males were mated with two virgin females,five batches were repeated to cover the whole spermatogenesis cycle to study the effects of cinnabar on germ cells at different stages of development.Females were sacrificed on the 17~(th)day of pregnancy and the number of pregnancies in female mice,embryo implanted,live births and stillbirths were recorded.Results The mean number of stillbirths in pregnant mice,the rate of pregnant mice with stillbirths and the embryonic mortality rate of the 0.80 g/kg·bw cinnabar group and the positive control group mated at 1~2 weeks were significantly higher than that of negative control,the mean number of live births of the positive control group mated at 1~3 weeks were significantly lower than that of negative control(F=7.39,F=13.15,F=3.63,F=5.99,F=1.16,χ^(2)=7.46,χ^(2)=12.23,χ^(2)=17.46,χ^(2)=29.00,χ^(2)=4.69,F=8.38,F=15.48,F=1.30,P<0.05).The dominant lethal rate of the 0.80 g/kg·bw cinnabar group mated at 2 weeks and the positive control group mated at 1~3 weeks were increased.The mating rate of the positive control and all treated groups were all in the normal ranges(χ^(2)=0.03~1.03,P>0.05).Conclusion Abnormal dominant lethal index appeared in cinnabar group under the the certain conditions of this study,which suggested that cinnabar may have mutagenic effect,the LOAEL of cinnabar on mice germ cells genotoxicity was 0.80 g/kg·bw.