冬凌草醇提物的肝肾毒性评价  

Hepatotoxicity and nephrotoxicity of the alcoholic extract from Rabodasia rubescens

作　　者：李寅超[1] 何永侠[1] 孙曼[1] 陈慧芳[1] 徐平华[1] 王随华[1] 可钰[1] 李惠举[1] 刘宏民[1] 

机构地区：[1]郑州大学药学院郑州大学药物安全性评价研究中心,河南郑州450001

出　　处：《中国医院药学杂志》2013年第10期764-769,共6页Chinese Journal of Hospital Pharmacy

基　　金：国家科技部"十一五"科技支撑计划子课题(编号:2006BAI06A03-03);郑州市科技攻关计划项目(编号:0910SGYS33389-5)

摘　　要：目的:通过连续30d灌胃给予冬凌草醇提物,观察其是否对大鼠产生蓄积性肝肾毒性反应,提供毒性的程度和可逆性,为开展后续的安全性评价提供参考。方法:选取80只大鼠,雌雄各半,体质量(200±20)g,按体质量分层随机分为4组,即冬凌草醇提物高、中、低剂量组和溶媒对照组,每组雌、雄动物各10只。各给药组大鼠分别灌胃给予冬凌草醇提物0.96,0.71,0.46g.kg-1的剂量,溶媒对照组灌胃等体积的CMC-Na(6g.L-1)。连续给药30d后停药恢复14d。分别于给药结束和恢复期结束时,各组雌雄动物分别剖杀1/2进行血液生化检查及系统尸检和组织病理学检查。实验过程中记录大鼠的一般状况、体质量、摄食量。结果:除高剂量组1只雄鼠死亡外,其余各组均无动物死亡。给药期间冬凌草醇提物高、中剂量组大鼠体质量减轻,精神状态差,竖毛,低剂量组和溶媒对照组大鼠一般状态良好。冬凌草醇提物高剂量组雄鼠血清ALT、BUN水平和中剂量组雌鼠血清BUN水平,均较溶媒对照组显著升高(P<0.05)。给药结束时,高剂量组与溶媒对照组比较雌雄大鼠肝脏体积增大,雄性大鼠肾脏湿重显著降低(P<0.05),恢复期结束时高剂量组雄鼠肝脏湿重较溶媒对照组明显减轻(P<0.01),左肾系数明显增加(P<0.05)。病理学检查显示,冬凌草醇提物中、高剂量组部分动物肝细胞肿大,肝窦变窄,灶性间质性肾炎,病变程度和病变频率与给药有剂量依赖性,停药14d上述病变基本恢复正常。溶媒对照组和冬凌草醇提物低剂量组大鼠肝肾未见明显异常。结论:冬凌草醇提物高剂量重复给药(30d)可能产生肝肾损伤作用,但其病变具有可逆性,病变程度与给药有剂量依赖性。OBJECTIVE To observe whether the alcoholic extract from Rabdosia rubescens could cause accumulative toxicity of the liver and kidney in rats,providing a reference for evaluation of the follow-up safety.METHODS 80 rats were selected,female,half male,body weight（200±20） g.They were randomly divided into 4 groups： Rabdosia rubescens alcohol extracts high,medium and low-dose groups and solvent control group.There were 10 female and male animals in each group.The rats were administered to give the Rabdosia rubescens alcohol extract 0.96 g·kg-1（equivalent to native herbs 20.84 g·kg-1）,0.71 g·kg-1（equivalent to native herbs 15.41 g·kg-1）,0.46 g·kg-1（equivalent to native herbs 9.99 g·kg-1） dose continuously for 30 days and recovery 14 days.At the end of the medication and recovery period,half of male and female animals in each group were sacrificed for blood biochemical examinations,system autopsy and histopathological examination and the rats＇ general conditions,body weight,food consumption were recorded.RESULTS Except one male animal of the high dose group died,there was no animal died in other groups.During the administration period,the high and medium dose of the Rabdosia rubescens alcohol extracts decreased the rats＇ body weight;the rats reacted slowly and erected hair.In Rabdosia rubescens alcohol extracts low-dose group and solvent control group,the rats were generally in good condition.The blood biochemical index（ALT,BUN） levels of male rats in the Rabdosia rubescens alcohol extracts high-dose group and the blood biochemical index（BUN） levels of female rats in the medium-dose all rised significantly higher（P0.05） than those of the solvent control group.At the end of the medication,compared to the solvent control group,the liver volume of male and female rats increased and the wet weight of the kidney of the male rat significantly reduced（P0.05） in high-does.At the end of the recovery period,compared to the solvent control group,the wet weight of the liver obviously red

关 键 词：冬凌草 醇提物 肝肾毒性 

分 类 号：R965.3[医药卫生—药理学]