盐酸西部曲明对小鼠生殖发育毒性的实验研究  

Studies of the Effects of Sibutramine Hydrochloride on Perinatal Development and Maternal Function in Mice

作　　者：胡渝华[1] 庞定国[1] 漆波[1] 雷琪[1] 游山[1] 刘玉清[1] 

机构地区：[1]四川大学华西公共卫生学院卫生毒理学研究室,成都610041

出　　处：《四川大学学报（医学版）》2004年第2期229-231,共3页Journal of Sichuan University(Medical Sciences)

摘　　要：目的　研究新药盐酸西部曲明在小鼠妊娠后期、分娩及哺乳期内摄入是否对母代妊娠、分娩、授乳 ,胎仔发育后期、幼仔新生期存活和生长发育有不良影响。方法　孕鼠随机分为 32 m g/ kg、2 .83mg/ kg、0 .2 5 m g/ kg三个受试物组和一个阴性对照组。母鼠从妊娠 15 d到分娩后 2 1d持续饮水内给药。观察并记录孕鼠的一般状况、分娩情况、哺乳情况 ,出生后仔鼠的窝平均生长指数、生理发育情况和神经行为发育情况等指标。结果　各受试物组与对照组相比较 ,一般状况、母鼠死亡率、异常分娩率、出生存活率、哺乳存活率、子代生长指数、子代各项生理发育指标、行为发育指标和断乳后食物利用率均无显著性差异 (P>0 .0 5 )。结论　盐酸西部曲明对小鼠生殖发育、神经行为发育没有不良影响 ;但在大大高于临床预期用药量的高剂量下 。Objective To detect adverse effects on the pregnant/lactating dams and on the development of the offspring following exposure to sibutramine hydrochloride of the dams from the closure of the hard palate through weaning. Methods Studies on the effects of this new drug on pre- and postnatal development, including maternal function of mice were conducted. The pregnant mice were randomly divided into four groups. The dose levels were 32 mg/(kg·d) (1/5 LD 50), 2.83 mg/(kg·d), 0.25 mg/(kg·d) for three groups respectively, and the fourth group was for negative control. Females were administered sibutramine hydrochloride in drink water from the closure of the hard palate (pregnant 15 d) to the end of lactation. Adverse effects on pregnant mice, pre- and postnatal deaths of offspring, altered growth and development, functional deficits in offspring were assessed.Terminal examinations included: necropsy (macroscopic examination) of all adults, abnormalities, live offspring at birth, body weight at birth, pre- and postweaning survival and growth/body weight, maturation, physical development, sensory functions and reflexes and behavior. Results The increase of death (above 10 %) of pregnant and lactating mice was observed in the group of 32 mg/(kg·d). No other adverse effects on the maternal animals and offspring were observed. Conclusion The data of these studies on mice showed no evidence for the reproductive toxicity to pregnant mice and the developmental toxicity to offspring induced by sibutramine hydrochloride.

关 键 词：盐酸西部曲明 生殖毒性 发育毒性 小鼠 

分 类 号：R96[医药卫生—药理学]