摘要
目的观察回春散对幼年大鼠生长发育产生的毒性和一般毒性反应,判断主要的毒性靶器官或靶组织及其损害的可逆性,确定无不良反应剂量,为临床儿科用药提供参考。方法实验用SPF级幼年SD大鼠(21d,刚断乳),设溶媒对照组,回春散低、中、高剂量组(0.4、1.2、3.6g/kg,分别为临床等效剂量的2.3、7.0、21.0倍)4组,经口灌胃给药,每天1次,连续4周。给药后每周1次测定动物体质量及摄食量,每两周1次测定顶臀长度,2、4、8周通过笼内观察、手持观察、开放场观察、反射评价、肌张力评价神经系统的发育毒性,期间一定时间点检查生殖系统发育指标。在给药结束(4周)后,取2/3动物采血解剖,进行血液学和血液生化指标等检测,同时进行眼科、骨髓、胫骨长度及病理学检查。恢复期4周结束后对剩余动物进行各项检查。结果给药期间和停药观察期间动物笼旁观察体质量及摄食量、眼科检查、血液学及血液生化检查、尿常规检查、胫骨长度和顶臀长度、神经系统及生殖系统发育指标、性激素(雌二醇和睾酮)水平、免疫球蛋白、大体解剖和各脏器的质量及脏器系数、组织病理学均未发现与药物相关的异常改变。结论回春散对幼年大鼠经口灌胃给药4周及停药4周未见发育毒性,也未见其他毒性反应,最大无毒性反应剂量为3.6g/kg(按小儿体质量12kg折算,以21d幼年大鼠体质量50g计,为临床小儿用剂量的108倍,等效剂量的21倍)。
Objective To investigate the development toxicity and general toxicity of Huichun Powder on juvenile rats,and evaluate the reversibility of major toxic target organs or tissues,and to determine the dose without adverse reactions,and to provide reference for clinical pediatric medication.Methods SPF-grade juvenile SD rats(21 d,just weaned)were administered orally once a day for 4 weeks in four groups:vehicle control group,Huichun powder low,medium and high dose group.The low,medium and high dose groups of Huichun powder(0.4,1.2,3.6 g/kg,respectively)were clinically equivalent doses(2.3,7.0,21.0 times).After administration,the animal′s body weight and food intake were measured once a week,and the top-buttock length was measured once every two weeks.The nervous system was evaluated through cage observation,hand-held observation,open field observation,reflex evaluation,and muscle tension at 2,4,and 8 weeks.During the developmental toxicity,check the reproductive system development indicators at a certain time point.At the end of the administration(4 weeks),2/3 of the animals were collected for blood dissection,and hematology and blood biochemical indicators were tested.At the same time,ophthalmology,bone marrow,tibia length and pathological examinations were performed.After the end of the recovery period of 4 weeks,the remaining animals were checked.Result Huichun powder was administered to newly weaned SD rats by oral gavage,once a day,after continuous administration for 4 weeks,the drug was discontinued for 4 weeks,and the animals were observed next to the cage during the administration and the period of discontinuation.Food intake,eye examination,hematology and blood biochemical examination,routine urine examination,tibia length and top buttocks length,nervous system and reproductive system development indicators,sex hormones(estradiol and testosterone)levels,immunoglobulin,general anatomy and various organs No drug-related abnormal changes were found in organ weight,organ coefficient,and histopathology.Conclusi
作者
吴兰生
罗红婷
谢越钡
梁金强
黄芝瑛
WU Lan-sheng;LUO Hong-ting;XIE Yue-bei;LIANG Jin-qiang;HUANG Zhi-ying(Guangdong Jianquan Pharmaceutical Technology Co.,Ltd.,Guangzhou Guangdong 510380;China Traditional Chinese Medicine Holdings Co.,Ltd.,Foshan Guangdong 528303;Drug Safety Evaluation Center,School of Pharmacy,Sun Yat-Sen University,Guangzhou Guangdong 510006)
出处
《世界中西医结合杂志》
2020年第8期1461-1466,共6页
World Journal of Integrated Traditional and Western Medicine
基金
国家卫健委研究课题示范项目。
关键词
回春散
幼年大鼠
毒性反应
Huichunsan Powder
Juvenile Rat
Repeated Dose Toxici
