乙烷硒啉对大鼠致畸敏感期毒性试验研究  

Toxicity Study of Ethaselen on Rats During Period of Sensitive Teratogenesis

作　　者：宋瑞霞[1] 林飞[2] 梁怿[2] 吕廉[2] 

机构地区：[1]中国疾病预防控制中心环境与健康相关产品安全所,北京100021 [2]中国药品生物制品检定所

出　　处：《预防医学情报杂志》2008年第4期241-244,共4页Journal of Preventive Medicine Information

基　　金：北京市科委快速追踪化学创新药物研究与开发重点专项(H020220060190)(2002-2005)创新【1(1)】抗肿瘤新药Eb研究开发;国家自然科学基金面上项目(30472036)(2004-2007)靶向硫氧还蛋白还原酶創新抗肿瘤药物Eb作用机理研究

摘　　要：目的观察乙烷硒啉对大鼠是否存在胚胎毒性和致畸毒性。方法采用Wistar大鼠,每组妊娠鼠>15只。试验设1000mg/kgbw、500mg/kgbw、250mg/kgbw和125mg/kgbw4个剂量组,同时设1个阳性对照组和1个溶剂对照组。在大鼠胚胎器官形成期连续灌胃给药10d(孕615d),在妊娠的第20天,处死妊娠鼠,计数黄体数、着床数、活胎数、早期死胎数(包括吸收胎)和晚期死胎数;观察胎仔性别、外观、称取胎重,并检查骨骼和内脏发育情况。结果给药>250mg/kgbw剂量组的孕鼠体重增长缓慢,胎仔的活胎率降低到94.9%以下、吸收胎率增加到4.5%以上,与溶剂对照组比较差异均有统计学意义(P<0.05或<0.01);黄体数、着床数、死胎数、胎仔体重、身长、尾长和胎仔性别等与溶剂对照组基本一致。给药各剂量组未见明显的骨骼畸形和内脏器官畸形。结论乙烷硒啉在>250mg/kgbw剂量时,对大鼠具有明显的母体毒性和胚胎毒性;在<500mg/kgbw剂量时,不存在骨骼、内脏器官的致畸毒性。Objective To observe whether there are embryonic and teratogenesis toxicity on rats disposed by different dosages of the ethaselen continuously during the period of organic formation. Methods The pregnant Wistar rats were divided into six groups, i. e. four dosage groups （1 000,500,250 and 125mg/kgbw）, one positive and one negative control groups. There were more than 15 pregnant rats in every group. The groups of drug samples were injected continuously via irrigate paunch every day for ten days （6 -15 days of pregnancy） during the period of organic formation. The numbers of corpus luteum, nidation, alive-embryo, forepart fetal death, advanced stage fetal death were counted after killing the pregnant rats at the twentieth day. After observed the sex, appearance and weight of embryonic rats, they were divided into two groups. In one group, the bones development was observed after ethanol fixing, potassium hydroxide melting, Alizarin Red staining and glycerin transparencing. In another group, the viscera development was observed after Bouins solution fixing under big-inspect-instrument. Results The body weight accretion was obviously lower, alive-embryo was decreased to 〈 94. 9%, fore- part fetal death was increased to 〉4. 5%, in 〉 250 mg/kgbw dosage groups of pregnant rats than those in negative control group （P 〈 0. 05 or 〈 0. 01 ）, but there were no differences in other indices. There were no obvious development abnormality in embryonic rats appearances, bones and viscera in every disposed dosage groups. Conclusion Ethaselen have matrix and embryonic toxicity at 〉 250 mg/kgbw dosage groups and have no bones and viscera obvious development abnormality under the dosage of 〈 500 mg/kgbw.

关 键 词：乙烷硒啉 大鼠 胚胎 生长发育 生殖毒性 

分 类 号：R965.3[医药卫生—药理学]