[关键词]
[摘要]
目的 以受精大鼠和家兔为实验系统,评价牛蒡子苷元对动物胚胎-胎仔发育的影响,为其药用价值的进一步开发提供参考。方法 100只受精雌鼠分为溶媒对照组和牛蒡子苷元高、中、低剂量(64、16、4 mg/kg)组,每组25只;72只受精雌兔分为溶媒对照组和牛蒡子苷元高、中、低剂量(25、10、4 mg/kg)组,每组18只。全部动物于妊娠第6天(GD6)开始给药,每天ip给药1次,大鼠连续给药至GD15,停药至GD20解剖检查,家兔连续给药至GD18,停药至GD29解剖检查。试验期间,每天观察动物一般状态,定期检测动物体质量和摄食量,解剖时计数卵巢黄体数量、检查着床数和活胎数,测量活胎顶臀长和尾长,检查活胎外观、内脏和骨骼。结果 给药期间,动物除给药方法导致的注射部位炎症反应外,其他未见异常体征变化;与溶媒对照组比较,牛蒡子苷元未引起大鼠和家兔体质量异常增长;母本动物受孕率、平均黄体数量和受精卵着床丢失率也未见异常改变;窝均活胎率、死胎率和吸收胎率,胎仔顶臀长和尾长也未见明显改变;也未见受试物导致的胎仔外观、内脏和骨骼畸形。结论 牛蒡子苷元未见潜在的大鼠和家兔胚胎-胎仔发育毒性。在本试验条件下,牛蒡子苷元大鼠和家兔胚胎-胎仔发育毒性的无明显损害作用剂量(NOAEL)分别为64和25 mg/kg。
[Key word]
[Abstract]
Objective To provide a reference for drug development of Arctigenin, the study is designed to evaluate the developmental toxicities of Arctigenin on embryo-fetal of rats and rabbits. Methods Totally 100 fertilized rats were divided randomly into vehicle control group, Arctigenin 4, 16, and 64 mg/kg groups, and 72 fertilized rabbits were divided randomly into vehicle control group, Arctigenin 4, 10, and 25 mg/kg groups. Animals were ip administered with Arctigenin from day 6 of pregnancy (GD6) once daily, rats were treated until GD15 and sacrificed on GD20, while rabbits were treated until GD18 and sacrificed on GD29. The clinical manifestation of animals was observed every day during test period, feed take and bodyweight were detected regularly. Corpora lutea number, implantation number, and living fetus number were counted. Lengths of fetus Crown-Rump and tail were measured and the appearance, skeleton, and viscera of fetus were detected. Results With the exception of inflammation caused by treated method, no apparent toxic reaction in pregnant animals was shown in all groups. Compared with vehicle control, rats and rabbits treated with Arctigenin had no abnormal change on maternal pregnancy rate, average corpora lutea number, average implantation loss rate, and average living fetus rate, and likewise, average lengths of fetus Crown-Rump and tail were normal. Moreover, rats and rabbits treated with Arctigenin had no malformation in fetus appearance, skeleton, and viscera compared with vehicle control. Conclusion Arctigenin has no potential developmental toxicities on embryo-fetal of rats and rabbits. Under the experimental conditions, the no observed adverse effect levels (NOAEL) of Arctigenin developmental toxicity on embryo-fetal of rats and rabbits are 64 and 25 mg/kg.
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[基金项目]
山东省自主创新及成果转化专项(2015ZDQJ05004)