摘要
目的考察单次和重复灌胃给予复方一枝蒿颗粒对离乳前SD大鼠(PND15,出生第15天)的影响,为其临床合理用药提供参考。方法选择5窝符合交叉抚育要求的母鼠及其幼鼠,进行交叉抚育分组,其中3窝按照母鼠的随机号分为溶媒对照组、复方一枝蒿颗粒70.4、88.0 g/kg组,单次给药后观察动物体征至14 d,剖检肉眼大体观察各脏器形态。选择20窝符合交叉抚育要求的母鼠及其幼鼠,各窝按照母鼠编号随机分为溶媒对照组、复方一枝蒿颗粒17.6、44.0和70.4 g/kg组,幼鼠PND15开始给药,连续28 d,检测指标包括一般观察、生长发育、眼科、行为学等指标,并进行组织病理学检查。结果单次给药毒性试验:给药第2天88.0 g/kg组3只动物死亡,70.4、88.0 g/kg组体重出现明显下降。重复给药毒性试验:70.4 g/kg组雌雄大鼠体重在给药第3天均低于溶媒对照组;给药期结束,雄鼠70.4 g/kg组顶臀长和胫骨长均低于溶媒对照组,雌雄大鼠44.0、70.4 g/kg组尿液BIL阳性率高于溶媒对照组,各剂量组雌雄鼠肝脏体比和脏脑比均高于溶媒对照组。结论复方一枝蒿颗粒离乳前SD大鼠单次给药最大耐受量(MTD)为70.4 g/kg,重复给药28 d最大无毒反应剂量(NOAEL)为44.0 g/kg。
Objective To investigate single dose and repetitive dose toxicity of compound Yizhihao particles on pre-weaning Sprague Dawley(SD)rats(postnatal day 15;PND15)and provide a reference for human clinical use.Methods Five litters of female rats and their offspring were selected that met the requirements of the fostering design.Three litters were randomly divided into solvent control,compound Yizhihao particles dosage groups(70.4,88.0 g/kg),according to the serial numbers of the female rats.A detailed observation of the rat,including examination of viscera morphology by naked eye,was conducted until day 14 post-drug administration.Simultaneously,20 female rats and their offspring were selected that met the requirements of the fostering design.Each litter was randomly divided into solvent control,lcompound Yizhihao particles dosage groups(17.6,44.0,70.4 g/kg)according to the serial numbers of the female rats.At PND15,compound Yizhihao particles was orally administered daily to the juvenile rats for 28 days,with recovery for 28 days after cessation.Parameters were examined including general condition,development index,ophthalmic examination,behavioral test,and histopathological examination.Results In the single dose toxicity study,three animals died in the 88.0 g/kg dose group at day 2 while the weights of both the 70.4,88.0 g/kg dose groups decreased significantly.In the repetitive dose toxicity study,compared with the solvent control group,the weights of both male and female rats in the 70.4 g/kg dose group were significantly decreased at day 3.After 28 days of treatment,a decrease in mean crown-rump length and tibia length were noted in the males of the 70.4 g/kg dose group.Urine bilirubin showed increases in the 44.0,70.4 g/kg dose groups.The ratio of liver and kidney weight to body weight and to brain weight in the17.6,44.0,70.4 g/kg dose groups for both male and female rats were higher than those in the solvent control group.Conclusions The maximum tolerated dose of compound Yizhihao particles in juvenile rats was 70.4 g/kg in a single dose toxicity study.The no observed adverse effect level was 44.0 g/kg in a 28 day repetitive dose toxicity study.
作者
田义超
周莉
庞聪
毛闪闪
崇立明
李俊
李艳
冷英莉
孙祖越
TIAN Yichao;ZHOU Li;PANG Cong;MAO Shanshan;CHONG Liming;LI Jun;LI Yan;LENG Yingli;SUN Zuyue(Hubei Topgene Biotechnology Co.,Ltd.,Wuhan Branch,Wuhan 430075,China;Shanghai Institute of Planned Parenthood Research,National Evaluation Centre for Toxicology of Fertility Regulating Drugs,Shanghai 200032;Xinjiang Yinduolan Uighur Medicine Co.,Ltd.,Urumqi 830013)
出处
《中国比较医学杂志》
CAS
北大核心
2020年第2期15-20,共6页
Chinese Journal of Comparative Medicine
基金
国家科技重大专项(2018ZX09201017-002)
上海市科委研发平台专项(17DZ2293600)
新疆维吾尔自治区科技厅十三五重大专项课题(2016A03005-4).
作者简介
第一作者:田义超(1987—),男,助理研究员,研究方向:新药临床前安全性评价。E-mail:tianyichao@topgenebio.com;第一作者:周莉(1968—),女,研究员,研究方向:药物生殖药理毒理学研究、新药非临床安全性评价。E-mail:zhoulijss@163.com;通信作者:孙祖越(1964—),男,研究员,研究方向:药物生殖药理毒理学研究、新药非临床安全性评价。E-mail:sunzy64@163.com
