藏药红花如意丸对大鼠胚胎-胎仔发育的影响  

Effect of Tibetan medicine safflower Ruyi pills on rat embryo-fetal development

作　　者：周莉[1,2,3] 崇立明[1,2,3] 何强 王蓉[1,2,3] 马爱翠[1,2,3] 闫晗[1,2,3] 徐斯翀[1,2,3] 孙祖越[1,2,3] 

机构地区：[1]上海市计划生育科学研究所药理毒理学研究室,中国生育调节药物毒理检测中心,上海200032 [2]国家人口和计划生育委员会计划生育药具重点实验室,上海200032 [3]复旦大学生殖与发育研究院,上海200032 [4]甘南佛阁藏药有限公司,甘南747000

出　　处：《中国新药杂志》2017年第1期77-83,共7页Chinese Journal of New Drugs

基　　金：上海市实验动物创新行动计划项目(14140901302);上海市男性生殖与泌尿疾病药物非临床评价专业技术服务平台(15DZ2290400)

摘　　要：目的:观察红花如意丸对SD大鼠胚胎-胎仔发育的影响,为临床用药提供参考。方法:不同剂量的红花如意丸(1,5和15 g·kg^(-1))在着床至硬腭闭合期间(gestation day 6~15,GD6~15)灌胃(ig)给予SD妊娠大鼠,纯化水和环磷酰胺分别作为溶媒对照和阳性对照;阳性对照组于GD12皮下注射给予环磷酰胺(15mg·kg^(-1));检测并记录母鼠体重、摄食量、孕鼠子宫肌张力、激素检测(雌二醇、孕酮和睾酮)、胚胎着床、胎仔吸收、以及对胎仔生长发育和畸形情况。结果:红花如意丸对孕鼠的妊娠结局(平均黄体数和死胎率等)和胎仔的外观、内脏和体格生长发育(窝均体重、身长、尾长和胎盘重)均未见明显影响;对母鼠的毒性主要表现为5和15 g·kg^(-1)组母鼠体重增长缓慢和高剂量导致的宫外增重减少;对胚胎-胎仔发育毒性表现为15g·kg^(-1)组活胎率降低,吸收胎率增加,以及5和15 g·kg^(-1)组胎仔胸骨节骨化点发育迟缓。结论:红花如意丸无致畸作用,对SD大鼠胚胎-胎仔发育毒性的最大无毒性反应剂量(no observed adverse effect level,NOAEL)为1 g·kg^(-1),是等效剂量的2.1倍,临床剂量的12.5倍。Objective： To investigate the potential reproductive toxicity of safflower Ruyi pills on embryofetal development in SD（Sprague-Dawley） rats,and provide reference for clinical medication. Methods： Various doses of safflower Ruyi pills were given to SD pregnant rats（1,5 and 15 g·kg^-1） by intragastric administration for the period from implantation to hard palate closure. Distilled water and cyclophosphamide were used as solvent control and positive control,respectively. The rats in the positive control group were intraperitoneally injected with cyclophosphamide at a dose of 15 mg·kg^-1 on GD12. The effects on maternal weight,food intake,and pregnant rat myometrium strip tension,hormone detection（estradiol,progesterone and testosterone）,implantation and fetal resorption as well as the effects on fetal physical growth and congenital malformations were recorded. Results：Safflower Ruyi pills had no adverse effects on the pregnancy outcome of SD rats（the average number of corpus luteum and stillbirth rate,etc.）,the appearance of the fetus,and the visceral and physical growth and development（body weight,body length,tail length and placental weight）. The maternal toxicities including lower maternal weight and lower extra-uterine weight gain were observed after exposure to 5 and 15 g·kg^-1 of safflower Ruyi pills. Fetal toxicities were observed in 15 g·kg^-1 group including decreased rate of live fetuses and increased rate of fetal resorption,and sternebra retardation was observed after exposure to 5 and 15 g·kg^-1of safflower Ruyi pills.Conclusions： Safflower Ruyi pills exhibited NOAEL（no observed adverse effect level） on embryo-fetal development for SD rats at the dose of 1 g·kg^-1,which is 2. 1 times of equivalent rat doses and 12. 5 times of clinical dose.

关 键 词：大鼠 胚胎-胎仔发育 红花如意丸 藏药 生殖毒性 

分 类 号：R285.5[医药卫生—中药学] R394.6[医药卫生—中医学]