目的 以受精大鼠和家兔為實(shí)驗(yàn)系統(tǒng)，評(píng)價(jià)牛蒡子苷元對(duì)動(dòng)物胚胎-胎仔發(fā)育的影響，為其藥用價(jià)值的進(jìn)一步開(kāi)發(fā)提供參考。方法 100只受精雌鼠分為溶媒對(duì)照組和牛蒡子苷元高、中、低劑量（64、16、4 mg/kg）組，每組25只；72只受精雌兔分為溶媒對(duì)照組和牛蒡子苷元高、中、低劑量（25、10、4 mg/kg）組，每組18只。全部動(dòng)物于妊娠第6天（GD6）開(kāi)始給藥，每天ip給藥1次，大鼠連續(xù)給藥至GD15，停藥至GD20解剖檢查，家兔連續(xù)給藥至GD18，停藥至GD29解剖檢查。試驗(yàn)期間，每天觀察動(dòng)物一般狀態(tài)，定期檢測(cè)動(dòng)物體質(zhì)量和攝食量，解剖時(shí)計(jì)數(shù)卵巢黃體數(shù)量、檢查著床數(shù)和活胎數(shù)，測(cè)量活胎頂臀長(zhǎng)和尾長(zhǎng)，檢查活胎外觀、內(nèi)臟和骨骼。結(jié)果 給藥期間，動(dòng)物除給藥方法導(dǎo)致的注射部位炎癥反應(yīng)外，其他未見(jiàn)異常體征變化；與溶媒對(duì)照組比較，牛蒡子苷元未引起大鼠和家兔體質(zhì)量異常增長(zhǎng)；母本動(dòng)物受孕率、平均黃體數(shù)量和受精卵著床丟失率也未見(jiàn)異常改變；窩均活胎率、死胎率和吸收胎率，胎仔頂臀長(zhǎng)和尾長(zhǎng)也未見(jiàn)明顯改變；也未見(jiàn)受試物導(dǎo)致的胎仔外觀、內(nèi)臟和骨骼畸形。結(jié)論 牛蒡子苷元未見(jiàn)潛在的大鼠和家兔胚胎-胎仔發(fā)育毒性。在本試驗(yàn)條件下，牛蒡子苷元大鼠和家兔胚胎-胎仔發(fā)育毒性的無(wú)明顯損害作用劑量（NOAEL）分別為64和25 mg/kg。

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.

山東省自主創(chuàng)新及成果轉(zhuǎn)化專項(xiàng)（2015ZDQJ05004）