巴戟天寡糖幼龄大鼠重复给药毒性研究  

Toxicity of Morinda Officinalis Oligosaccharides in Juvenile Rats After Repeated Administration

作　　者：赵曼曼 杨海润[2] 杨硕 魏胜焦 杨莹[1] 屈哲[1] 晁利平 王三龙[1] 耿兴超[1] 吴笑如 周晓冰[1] ZHAO Manman;YANG Hairun;YANG Shuo;WEI Shengjiao;YANG Ying;QU Zhe;CHAO Liping;WANG Sanlong;GENG Xingchao;WU Xiaoru;ZHOU Xiaobing(National Institutes for Food and Drug Control,National Center for Safety Evaluation of Drugs,Beijing Key Laboratory of Non-Clinical Drug Safety Evaluation and Research,Beijing 100176,China;Research Institute of Beijing Tongrentang Co.,Ltd.,Beijing 100011,China;Guizhou Institute for Food and Drug Control,Guiyang 550004,China)

机构地区：[1]中国食品药品检定研究院,国家药物安全评价监测中心,药物非临床安全评价研究北京市重点实验室,北京100176 [2]北京同仁堂股份有限公司科学研究所,北京100011 [3]贵州省食品药品检验所,贵阳550004

出　　处：《中国现代应用药学》2024年第22期3100-3106,共7页Chinese Journal of Modern Applied Pharmacy

基　　金：中国食品药品检定研究院中青年发展研究基金项目(2020C1)。

摘　　要：目的研究巴戟天寡糖连续给药6周对幼龄SD大鼠生长发育的影响,为巴戟天寡糖应用于青少年的安全性提供参考。方法将120只26日龄SD大鼠(雌雄各半)随机分为辅料对照组(空白辅料)及巴戟天寡糖低剂量组(50 mg·kg^(-1))、中剂量组(160 mg·kg^(-1))和高剂量组(500 mg·kg^(-1)),重复灌胃给予辅料或巴戟天寡糖混悬液,每日1次,给药体积15 mL·kg^(-1),给药期6周,恢复期4周。实验期间进行临床症状、体质量及摄食量、血液学及血清生化、尿液指标测定及功能观测组合试验(functional observation battery,FOB),解剖测定胫骨长度、骨密度,取主要脏器称重并进行组织病理学检查。结果与辅料对照组比,巴戟天寡糖处理组大鼠临床症状、体质量及摄食量、血液学及血清生化、尿液指标、FOB、胫骨长度、骨密度、脏器质量未见明显差异,未见巴戟天寡糖相关组织病理学改变。结论在本实验条件下,幼龄SD大鼠灌胃给予巴戟天寡糖6周,未见不良反应剂量为500 mg·kg^(-1),按公斤体质量折算约为人拟用剂量(10 mg·kg^(-1))的50倍。与成年动物相比,无增加的特殊安全风险。OBJECTIVE To study the effects of continuous administration of Morinda officinalis oligosaccharides(MOO)for 6 weeks on the growth and development in juvenile SD rats,and to provide a reference for the safety of MOO application in adolescents.METHODS One hundred and twenty juvenile SD rats,half male and half female,were randomly divided into excipient control group(blank aexcipient),and MOO low(50 mg·kg^(-1)),medium(160 mg·kg^(-1)),and high dose groups(500 mg·kg^(-1)).Excipient or MOO suspension was given by repeated intragastric administration,intragastric volume was 15 mL·kg^(-1),once daily for 6 weeks with a 4-week recovery phase.Clinical symptoms,body weight and food intake,hematology and serum biochemistry,ophthalmology,urine indexes and functional observation battery(FOB)were performed during the trial.Dissected and measured the length and bone density of the tibia,weighed the major organs,and performed histopathological examination on the tissue.RESULTS Compared with the excipient control group,there were no significant differences in clinical symptoms,body weight and food intake,hematology and serum biochemistry,ophthalmology,urine indexes,FOB,tibial length,bone density and organ weights,and no histopathological changes were observed in the MOO treatment groups.CONCLUSION Under the conditions of this experiment,juvenile SD rats were orally administered by MOO for 6 weeks.A total of 500 mg·kg^(-1)is the dosage without obvious adverse effect and approximately 50 times of the planned clinical dose.No additional safety risks are exsisted compared to adult animals.

关 键 词：巴戟天寡糖 幼龄大鼠 生长发育 安全性 

分 类 号：R285.5[医药卫生—中药学]