甘氨双唑钠对大鼠的致畸性评价

An evaluation of teratogenesis of glycididazolum natrium in Sprague-Dawley rats

目的：研究甘氨双唑钠（ＣＭＮａ）的致畸性。方法：采用传统致畸学试验方法，检测了ＣＭＮａ对Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ孕鼠在致畸敏感期的潜在毒性。试验设１３９．９，２７９．０和１３９９．０ｍｇ／ｋｇ３个剂量组（分别相当于１／２０，１／１０和１／２ＬＤ５０），同时设对照组（生理盐水），采用尾静脉注射给药。结果：孕鼠接受ＣＭＮａ后，母体体重减轻，并随剂量的增大而有剂量－效应关系。高剂量（１３９９．０ｍｇ／ｋｇ）组吸收胎增多，活胎率和平均每窝活胎数降低，并有一定程度的胎鼠畸形，总畸形率达９．４％。同时还显示ＣＭＮａ在２７９．０ｍｇ／ｋｇ剂量时有母体毒性和胚胎毒性，但无致畸作用；在１３９．９ｍｇ／ｋｇ剂量时，仅有母体毒性而无胚胎毒性和致畸作用。结论：该药在临床推荐应用剂量下使用比较安全。

Objective: To study the teratogenesis of glycididazolum natrium. Methods: Conventional teratogical experiment in vivo with SD rats was carried out. The compound was injected into pregnant rats through tail veins at the dosage of 139. 9, 279. 0 and 1 399. 0 mg/kg(equal to 1/20, 1/10 and 1/2 LD50) respectively; at the same time, normal saline was used for the negative control group. Results: The body weights of pregnant rats reduced after injection, and the changes of body weight were dose-dependent(P<0. 05, P<0. 01 ). At the dosage of 1 399. 0 mg/kg, the numbers of absorbed fetal went up, the rates of live fetus and the mean numbers of live fetus per litter went down, with the fetal malformations, 9. 4% total malformation rates and embryo toxicities. It showed maternal and embryo toxicities and no malformation effects in the 279 mg/kg group, while it showed no embryo toxicities and malformation effects but maternal toxicites in 139. 9 mg/kg group. Conclusion: The drug will be safe if it is administered under the clinic dosage recommended.