朱砂的胚胎毒性研究

目的:观察朱砂在小鼠妊娠中晚期、妊娠前与妊娠全期给药对小鼠胚胎的影响.方法:分2批试验进行研究,分别为妊娠中晚期给药试验和妊娠前与妊娠全期给药试验.每批试验均采用ICR小鼠分成4组:对照组和朱砂0.08,0.4,4.0 g·kg~(-1)剂量组.妊娠中晚期于孕后第6天开始给药一直给药至孕后第19天(D6～D19);妊娠前及妊娠全期给药试验则于交配前14 d至妊娠后19 d持续给药.2批实验均于妊娠期第20天行剖腹产,称量胎鼠体重,记录胎鼠数目、吸收胎、死胎、活胎等,同时观察胎仔外观有无异常.将每窝的胎仔分成二部分,1/3进行Bouin染液固定及染色,用于器官检查;另2/3进行骨骼染色,用于骨骼观察.结果:小鼠妊娠后D6～D19灌胃给药时,朱砂3个剂量组对胚胎发育无显著影响,活胎数、死胎数和吸收胎数量均与对照组比较无显著差异.胎仔外观检查、内脏检查、骨骼检查均未见明显畸形.交配前14 d至妊娠后第19天持续灌胃给予朱砂0.4,4.0 g·kg~(-1)·d~(-1),其流产率、吸收胎率较对照组稍高,但无显著性差异和剂量依赖关系.朱砂各剂量组的胎仔外观检查和内脏检查均未见明显异常.骨骼检查显示,朱砂可造成一定程度的骨骼畸形,其中0.4,4.0 g·kg~(-1)·d~(-1)剂量组骨骼畸形率较高,分别达到46.7%和77.8%.结论:妊娠中晚期用药对胚胎发育无显著影响,此时期胚胎对朱砂的敏感性较低;妊娠前以及妊娠早期使用朱砂(≥0.08 g·kg~(-1)·d~(-1),相当于临床5倍量)可能对胎儿造成危害,并随剂量增大作用有增高趋势.

Study on embryo toxicity of Cinnabaris

Objective: To observe the effect of Cinnabaris on mouse embryos after pregnant mice were treated by Cinnabaris in different periods of pregnancy. Method: Two separate experiments were performed: First, Cinnabaris was orally given into pregnant mice at the doses of 0.08, 0.4, 4.0 g·kg^-1 from D6 to D19 after pregnancy; Second, Cinnabaris was orally given into mice at the same doses mentioned above from D14 prior to pregnancy until D19 after pregnancy. All animals were sacrificed on D 20 of pregnancy by caesarean section. The numbers of survival,dead and absorbed fetuses were calculated and the survival fetus weight was measured. The survival fetuses were treated by two methods: One third survival fetuses were fixed and stained by Bouin solution for organ examination and the remaining two thirds fetuses were stained for skeleton examination. Result: No obvious embryo toxicity was observed in the first experiment at Cinnabaris dose levels of 0.08, 0.4, or 4 g·kg^-1·d^-1. There was no significant effect on embryonic development and the numbers of the survival, dead and absorbed fetus. No obvious malformations on appearance, organ, and skeleton examination of fetuses were found. The second experiment showed that the rates of abortion and absorbed fetus in 0.4, 4 g·kg^-1·d^-1 Cinnabaris group were higher but without statistical significance compared with control group. Appearance and organ examination of Cinnabaris groups fetus showed no obvious malformation, but skeleton malformation was found in 0.4, 4 g·kg^-1·d^-1 groups (the rates of skeleton malformation were 46.7% and 77.8%, respectively). Conclusion: No obvious embryonic development toxicity was observed when Cinnabaris was orally given in intermediate and late pregnant period, but the embryos in the early stage of pregnancy was more sensitive to Cinnabaris. When Cinnabaris was given prior to pregnancy until the whole period of pregnancy, it may be harmful for the fetuses at above the dose level 0.08 g·kg^-1·d^-1 (equivalent to 5 times clinical intake dose), both in a dose-dependent manner.