芩香清解口服液对4日龄大鼠的发育毒性  

Developmental toxicity of Qinxiang Qingjie oral solution for 4-day-old young rats

作　　者：郭健敏 张文强 邓应华 蒙飞彪 谢松强[2] 梁纯[3] 杨威 GUO Jianmin;ZHANG Wenqiang;DENG Yinghua;MENG Feibiao;XIE Songqiang;LIANG Chun;YANG Wei(Guangdong Lewwin Pharmaceutical Research Institute Co.,Ltd.,Guangdong Provincial Key Laboratory of Drug Non-clinical Evaluation and Research,Non-clinical Evaluation Sub-center for Traditional Chinese Medicine of National Engineering Research Center for Modernization of Traditional Chinese Medicine,Guangdong Engineering Research Center for Innovative Drug Evaluation and Research,Guangzhou 510990,China;School of Pharmacy,Henan University,Kaifeng 475000,China;Division of Life Sciences,Hongkong University of Science and Technology,Hongkong 999077,China)

机构地区：[1]广州湾区生物医药研究院,广东莱恩医药研究院有限公司,广东省药物非临床评价研究企业重点实验室,国家中药现代化工程技术研究中心中药非临床评价分中心,广东省创新药物评价与研究工程技术研究中心,广东广州510990 [2]河南大学药学院,河南开封475000 [3]香港科技大学生命科学部,中国香港999077

出　　处：《中国药理学与毒理学杂志》2023年第12期904-913,共10页Chinese Journal of Pharmacology and Toxicology

基　　金：国家科技重大专项(2018ZX09721003-009-025);广东省实验室建设项目(2023B1212070029);广东省重大人才工程项目(210183503006);广东省重点领域研发计划(2020B1111030005)。

摘　　要：目的系统考察芩香清解口服液(QXQJ)对4日龄(PND_(4))大鼠生长发育的影响。方法采用交叉抚育法对PND2大鼠进行数量和性别调整,随机分为溶剂对照组及QXQJ 3.45,10.35和28.05 g·kg^(-1)组。PND_(4)起每天ig给予QXQJ,溶剂对照组给予纯水,每天1次,连续给药18 d。给药结束后恢复观察3周。实验期间对各组大鼠一般状况、体重、生长发育、体格、骨骼、血液学和凝血等指标进行检查。结果QXQJ连续给药18 d对幼龄大鼠摄食量、生长发育、神经反射、自发行为、血液学、凝血、血液生化、免疫、生长激素和组织病理等检查指标均未见明显影响。PND5起,QXQJ 10.35和28.05 g·kg^(-1)组幼龄大鼠出现黄棕色软便或稀便以及腹部膨大症状,这些症状于PND_(22)基本恢复;28.05 g·kg^(-1)组幼龄大鼠于PND7起体重、顶臀长、尾长和四肢长较溶剂对照组明显偏低(P<0.05),停药1周后恢复;28.05 g·kg^(-1)组幼龄大鼠PND_(22)骨比重和骨密度显著低于溶剂对照组(P<0.05),PND_(4)2时基本恢复。结论QXQJ可导致未断乳幼龄大鼠出现黄棕色软便或稀便及腹部膨大等消化不良症状,继而影响体格发育,停药或离乳后基本恢复;QXQJ对PND_(4)大鼠连续给药18 d发育毒性的无不良反应剂量(NOAEL)为3.45 g·kg^(-1)。OBJECTIVE To investigate the effects of Qinxiang Qingjie oral liquid(QXQJ)on growth and development after repeated administration of 18 d to postnatal day 4(PND_(4))rats.METHODS The number and sex of PND2 pups were adjusted using the cross-breeding method.These pups were ran⁃domly divided into the normal control,QXQJ 3.45,10.35 and 28.05 g·kg^(-1)groups.PND_(4),juvenile rats were ig given QXQJ every day,while the normal control group was given pure water,once a day,for 18 d,before observation of 3 weeks was resumed.During the experiment,the general condition,body mass,growth and development,physique,bone,hematology and coagulation of the rats in each group were detected.RESULTS 18 d after continuous administration of QXQJ,there was no obvious effect on the food intake,growth and development,nerve reflex,spontaneous behavior,hematology,coagula⁃tion,blood biochemistry,immunity,growth hormone,histopathology and other examination indexes of juve⁃nile rats.From PND5,juvenile rats in the QXQJ 10.35 and 28.05 g·kg^(-1)groups developed yellow-brown soft or loose stools and abdominal distention,but the symptoms generally recovered at PND_(22).The body mass,top-rump length,tail length and limb length of the juvenile rats in the 28.05 g·kg^(-1)group were significantly lower at PND7(P<0.05),but recovered one week after drug withdrawal.The bone mineral specific gravity and bone mineral density of the 28.05 g·kg^(-1)group were significantly lower than those of the normal control group at PND_(22)(P<0.05),but there was no significant difference at PND_(4)2.CONCLU⁃SION QXQJ can cause such indigestion symptoms as yellow brown soft stool or loose stool and abdominal enlargement in unweaned juvenile rats,thus affecting the physical development indicators of rats,but the symptoms can recover after withdrawal of medication or withdrawal from milk.The no observed adverse effect level(NOAEL)of QXQJ administered to 4-day-old rats for 18 d is 3.45 g·kg^(-1).

关 键 词：芩香清解口服液 幼龄大鼠 重复给药 发育毒性 

分 类 号：R285.1[医药卫生—中药学]