去壁灵芝孢子粉幼龄大鼠安全性评价研究  

Safety evaluation of wall-removed Ganoderma lucidum spore powder in juvenile rats

作　　者：吕晗莹 宋翼升 王汉波 李振皓 徐靖 张城达 杨倩 刘靖 谢锋 黄敏聪 陈云祥 张立将 LYU Hanying;SONG Yisheng;WANG Hanbo;LI Zhenhao;XU Jing;ZHNAG Chengda;YANG Qian;LIU Jing;XIE Feng;HUANG Mincong;CHEN Yunxiang;ZHANG Lijiang(Center of Safety Evaluation,Hangzhou Medical College(Zhejiang Academy of Medical Sciences),Hangzhou 310053,China;Jinhua Shouxiangu Pharmaceutical Co.,Ltd.,Jinhua 321299)

机构地区：[1]杭州医学院(浙江省医学科学院)安全性评价研究中心,杭州310053 [2]金华寿仙谷药业有限公司,浙江金华321299

出　　处：《中国比较医学杂志》2021年第7期21-30,共10页Chinese Journal of Comparative Medicine

基　　金：浙江省重点研发计划项目(2020C03053,2021C03077);浙江省基础公益研究计划项目(LGF18H310004);浙江省实验动物科技计划项目(2018C37127)。

摘　　要：目的研究去壁灵芝孢子粉6周重复给药对幼龄大鼠各系统发育的影响及其毒性反应。方法24日龄(postnatal day,PND24)幼龄SD(Sprague-Dawley)大鼠128只,采用体重均衡法分为溶媒对照组、低剂量组、中剂量组和高剂量组,每组32只,雌雄各半,经口灌胃分别给予纯水、去壁灵芝孢子粉0.8、1.8和4.0 g/kg剂量,给药体积均为10 mL/kg,每天给药1次,连续给药6周(42 d),于停药次日、停药4周分别剖检每组雌雄大鼠10/16只、6/16只;检测常规毒性指标和生长发育、骨骼发育、行为学、性激素、免疫系统发育等指标。结果去壁灵芝孢子粉各剂量对幼龄SD大鼠临床症状、体重、摄食、性征发育、行为学、血液学、血清生化学、眼科、生长激素、性激素、骨骼系统发育、免疫学、组织病理学等指标均未见明显毒性影响;仅出现以高剂量为主的雌雄大鼠部分尿液指标可逆性异常(停药4周后恢复正常),考虑与供试品成分或其代谢产物经尿液排泄有关;各剂量组水迷宫实验中潜伏期时间减少、空间探索测定目标象限内时间百分比增加,提示学习记忆能力增强,考虑不排除可能与其药理学作用有关。结论去壁灵芝孢子粉对幼龄SD大鼠未见明显毒性反应,未观察到不良反应剂量(no-observed adverse effect level,NOAEL)为4.0 g/kg。Objective To explore the effects and toxicity of repeated administration of wall-removed Ganoderma lucidum spore powder for 6 weeks on the development of various systems in juvenile rats.Methods One hundred twenty-eight juvenile SD rats aged 24 days(postnatal day,PND24)were divided into vehicle control,low-dose,medium-dose and high-dose groups by the weight balance method.Each group was composed of 32 rats(half male and half female),and received pure water or wall-removed Ganoderma lucidum spore powder 0.8,1.8 and 4.0 g/kg doses by gavage,respectively,each in a volume of 10 mL/kg,once a day for 6 consecutive weeks(42 d).The day after drug withdrawal and 4 weeks after drug withdrawal,10/16 and 6/16 rats in each group were necropsied,and routine toxicity indicators and indicators of growth and development,bone development,behavior,sex hormones,immune system development,and other indicators were detected.Results Each dose of wall-removed Ganoderma lucidum spore powder had no significant toxic effects on the clinical symptoms,weight,food intake,sexual development,behavior,hematology,serum biochemistry,ophthalmology,growth hormones,sex hormones,skeletal system development,immunology,histopathology,or other indicators of juvenile SD rats.However,the rats in the high-dose group had reversible abnormalities in some urine indicators(all returned to normal after 4 weeks of drug withdrawal),which was considered to be related to the urine excretion of the test product components or their metabolites.In the water maze test of each dose group,the incubation period decreased,and the percentage of time in the target quadrant,as measured by space exploration,increased,suggesting that the learning and memory ability was enhanced,which may be related to its pharmacological effects.Conclusions Wall-removed Ganoderma lucidum spore powder has no obvious toxic effects in juvenile SD rats,and the NOAEL was 4.0 g/kg.

关 键 词：去壁灵芝孢子粉 儿科药物 幼龄动物试验 重复给药毒性 

分 类 号：R-33[医药卫生]