金丝桃苷对Wistar大鼠重复灌胃给药的毒性研究  

Toxicity of hyperoside after long-term oral administration in Wistar rats

作　　者：艾国[1,2] 黄正明[2] 王德文[1] 张海艇[3] 

机构地区：[1]军事医学科学院放射与辐射医学研究所,北京100850 [2]解放军302医院药学部,北京100039 [3]山东大学新药评价中心,济南250100

出　　处：《中国新药杂志》2012年第23期2811-2816,2828,共7页Chinese Journal of New Drugs

基　　金：国家自然科学基金(30572350);国家中医药管理局新药开发专项(DIX005A)

摘　　要：目的:观察金丝桃苷对大鼠的长期毒性反应,评价金丝桃苷的安全性,为临床剂量的拟定提供依据。方法:健康Wistar大鼠160只,雌雄各半。按体重随机分为对照组和低、中、高(30,175,1000 mg.kg-1.d-1)剂量组,每周给药6 d,连续给药6个月。停药后留取部分动物继续观察1个月。分阶段考察大鼠的一般症状、体重、耗料量、血液学指标、血清生化学指标,动物剖检,对主要脏器进行称重、计算脏器系数,进行组织病理学检查。结果:长期毒性实验中与同期对照组比较,金丝桃苷低、中、高3个剂量组动物行为活动、体重增长、耗料量等均未见明显异常,血液学指标、血液生化指标、脏器系数及病理组织学检查发现肾脏是可能的毒性靶器官,但肾脏损害是可逆的,停药后可以恢复正常。结论:金丝桃苷具有较好的安全性,肾脏是可能的毒性靶器官,但损害是可逆的,建议临床使用时定期进行血液学和肾功能指标监测。Objective： To investigate the chronic toxicity of hyperoside in rats for evaluating its safety and providing a recommendation in defining its clinical dose. Methods： Wistar rats into four groups of 40 animals each （20 per sex）. They were administered wi n=160） were randomly divided hyperoside 30, 175 and 1 000 mg. kg - 1. d - 1 by gavage for 6 months followed by subsequent 1 month recovery period ; 1% aqueous carboxymethyl- cellulose was used as the control. Mortality, clinical signs, body weight changes, food consumption, hematological and biochemical parameters, gross findings, organ weights and histological markers were monitored during the do- sing and recovery periods. Results： Compared with normal control group, no significant differences were observed in rats＇ behaviors, food-intake, weight gain and related examination indexes among the treatment groups. Hematolo- gy index, blood biochemical index, viscera coefficient and histological examination indicated that kidney was possi- ble toxic target organs but the damage was reversible. Conclusion： In general, hyperoside has a better safety. Kid- ney is possible toxic target organs, but the damage is reversible and can return to normal after withdrawal. We sug- gest that regular hematology and kidney function index monitoring are necessary when hyperoside is clinically used.

关 键 词：金丝桃苷 大鼠 长期毒性 

分 类 号：R961[医药卫生—药理学]