牛蒡子苷元对大鼠生育力与早期胚胎发育毒性的研究

Fertility and Early Embryo Developmental Toxicity of Arctigenin in Rats

目的以SD大鼠为实验系统评价牛蒡子苷元的生育力与早期胚胎发育毒性。方法 SD大鼠按照体重随机分为溶媒对照组和牛蒡子苷元4、16、64 mg·kg^(-1)三个剂量组,每组50只,雌雄各半。全部动物皮下注射给予对应药物,每日1次,给药体积2 mL·kg^(-1)。雌雄大鼠分别给药10wk和2 wk后将动物按照1:1比例合笼交配。动物交配期间持续给药,交配成功雌鼠继续给药至妊娠第6天(GD 6),交配成功雄鼠持续给药直至处死。试验期间,每日观察动物一般体征,定期检测动物体重和摄食量;雄鼠于交配成功后1 wk处死,检查精子质量和称量生殖器官重量;雌鼠于GD 15处死,检查黄体数、着床数、活胎数、吸收胎数和死胎数,称量子宫和卵巢重量。结果给药期间,各组均可见给药导致的给药部位刺激反应,牛蒡子苷元16、64 mg·kg^(-1)剂量组各有1只动物因药物毒性死亡;与溶媒对照组相比较,牛蒡子苷元各剂量组体重和摄食量均未见异常变化,动物交配天数、交配率和雌鼠受孕率、雄鼠精子质量和雌鼠妊娠结局均未见异常改变。结论在本实验条件下,牛蒡子苷元未见大鼠生育力与早期胚胎发育毒性,其未观察毒性剂量(NOAEL)为64 mg·kg^(-1)。

Objective To observe the toxicity effect of arctigenin on rat fertility and early embryo development in SD rats. Methods SD rats were divided into solvent control group and arctigenin 4, 16, 64 mg·kg-1 three dose groups, 25 animals per sex per group. Prior to mating, male rats were treated 10 weeks and female rats were treated 2 weeks respectively by subcutaneous injection with volume 2 mL · kg- 1 once a day. Within each treatment group, the male and female rats were co-housed （1：1） until evidence of mating was seen or for 2 consecutive weeks. During cohabitation period, total animals were continuously treated. After successful mating, female rats still were treated until day 6 of pregnancy and male rats were kept treating until euthanized. Chnical observations, body weights and food consumption were recorded routinely. Male rats were euthanized 1 week after successful mating, then sperm quality and reproductive organs wereinspected;femaleratswereeuthanizedonday15ofpregnancy, thenthecorporaluteum number, implantation number, viable fetuses number, absorbed fetuses number, dead fetuses number, uterus and ovary weight were inspected. Results During treating times, stimulation of drug delivery site were seen on all groups animals, arctigenin 16, 64 mg·kg -1 dose group caused 1 animal death respectively. Body weights and feed consumption in all arctigenin treatment groups were not significantly different when compared with the solvent group. There had no abnormal changes on animal precoital interval, mating index, gestation index, sperm quality of male rats and pregnancy outcome of female rats. Gonclusion Under this experimental environment, arctigenin has no significant toxicity on rat fertility and early embryo development, and the no observed adverse effect level（NOAEL）is 64 mg·kg-1.