水沉对益母草醇提物的小鼠急性毒性及毒靶器官的影响  

Influence of Water Precipitating on Acute Toxicity and Toxicity Target Organs of Alcohol Extracts from Herba Leonuri in Mice

作　　者：孙玲 李晓宇[2] 孙晓倩[3] 窦立雯 石亮[3] 赵红[4] 孙蓉[2] 

机构地区：[1]山东省药学科学院,山东济南250101 [2]山东省中医药研究院,山东济南250014 [3]山东中医药大学,山东济南250355 [4]中国人民解放军海军总医院,北京10004

出　　处：《中国药物警戒》2015年第12期711-716,726,共7页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金项目(81450021);山东省自主创新和成果转化项目(2014ZZCX02104)

摘　　要：目的比较水沉工艺对益母草醇提物小鼠急性毒性的影响及其毒性靶器官损伤程度的差异性。方法运用紫外分光光度法测定不同样品中益母草总生物碱的含量，急性毒性实验法对其急性毒性进行比较，记录其毒性症状、累积死亡数和小鼠体重变化，并于药后7天，取血，检测血液生化指标，取肝脏、肾脏称重，并计算脏器系数和进行病理组织学检查。结果益母草醇提物、醇提水沉物中总生物碱含量分别为0．82％和0．65％，益母草醇提物LD。按含生药量计算为118．68g·kg^-1，相当于临床70kg人日用量的276．9倍；95％可信限为112．84～124．89g·kg^-1，相当于临床70始人日用量的263．3～291．4倍。益母草醇提水沉物的MLD为433．20g·kg^-1，相当于临床70埏人日用量的1010．8倍。益母草醇提和醇提水沉物均可导致小鼠BUN、Cr水平明显升高（P〈0．001），肾脏系数升高，经统计学检验与正常对照组比较呈现不同程度的显著性差异；醇提物与醇提水沉物比较，醇提1～4组小鼠BUN、Cr水平升高，呈现不同程度的显著性差异，肾脏系数明显升高，经统计学检验，呈现不同程度的显著性差异；益母草醇提1～2组和醇提水沉物均可导致ALT、AST水平升高，经统计学检验与正常对照组比较呈现不同程度的差异性，醇提1组可导致肝脏系数升高，有非常显著性差异（P〈0．01）；醇提物与醇提水沉物比较，醇提1-2组的ALT、AST水平和肝脏系数升高，呈现不同程度的显著性差异。肝、肾病理表明，小鼠肝、肾组织未见明显病理改变。结论急性毒性试验显示益母草提取物的毒性靶器官主要为肾脏、肝脏，表现为BUN、Cr水平的显著增高和ALT、AST水平的增高和肝、肾脏系数的增加，其中肾脏毒性重于肝脏，益母草醇提物毒性大于醇提水沉物．结合益母草醇提物和醇提水沉的总碱含量数据�Objective To study the influence of water precipitating on alcohol extracts from Herba Leonuri for acute toxicity and damage degree of toxicity target organs in mice. Methods UV spectrophotometry was used to measure the content of total alkaloids and the method of acute toxicity was used to compare the difference of acute toxicity between different alcohol extraction processes, and its toxic symptoms, cumulative mortality and weight change in mice were recorded. Seven days after administration, blood was taken, the contents of serum biochemical indicators were detected, livers and kidneys were taken for organ coefficient. Results The contents of total alkaloids in the alcohol extracts and water precipitated alcohol extracts of Herba Leonur/were separately 0.82% and 0.65%. The LD50 of alcohol extracts from Herba Leonuri is 118.68 g·kg^-1, which is equal to 276.9 times of human daily dried medicinal herb dose.The 95% confidence interval is 112.84-24.89 g·kg^-1, which is equal to 263.3-291.4 times of human daily dried medicinal herb dose. The MLD of water precipitated alcohol extracts from Herba Leonur/is 433.20 g·kg^-1, which is equal to 1 010.8 times of human daily dried medicinal herb dose. The alcohol extracts and water precipitated alcohol extracts of Herba Leonuri all could lead to significant increase （P 〈0.001） of mice＇s BUN and Cr levels. Compared with normal control group, kidney coeffcient increased significantly, and the statistical tests showed varying degree difference. Compared with water precipitated alcohol extracts of Herba Leonuri, the BUN and Cr levels increased in group 1-4 of alcohol extracts, and the statistical tests showed varying degree difference. Kidney coefficient increased significantly, and the statistical tests showed varying degree difference. The group 1-2 of alcohol extracts and water precipitated alcohol extracts from Herba Leonuri could result in increased ALT and AST. Compared with normal control group, the statistical tests showed the varying degree difference. Group

关 键 词：益母草 水沉 醇提物 急性毒性 靶器官 

分 类 号：R992[医药卫生—毒理学] R282[医药卫生—药学]