薯蓣皂苷致肝毒性的初步研究  

Preliminary study on hepatotoxicity induced by dioscin

作　　者：周倩[1] 姚广涛[1] 金若敏[1] 

机构地区：[1]上海中医药大学药物安全评价研究中心,上海201203

出　　处：《中药药理与临床》2013年第2期29-32,共4页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家重点基础研究发展计划(973计划)(2009CB522807);国家"重大新药创制"科技重大专项项目(2009ZX09502-002)

摘　　要：目的:通过体外实验考察薯蓣皂苷Dioscin(Dio)对肝脏的毒性。方法:①采用MTT法检测肝细胞活力;②以不同浓度的薯蓣皂苷与人肝细胞(L-02)共培养后,检测细胞上清液中的丙氨酸转氨酶(ALT),碱性磷酸酶(ALP)和乳酸脱氢酶(LDH)含量,并采用倒置相差显微镜观察细胞形态;③采用Hoechst-PI染色法观察细胞凋亡;④KM种小鼠分为正常组和给药组,给药组小鼠每天尾静脉注射10μg/ml薯蓣皂苷,连续7d,观察血清肝功能和肝组织病理学变化。结果:①MTT法显示,薯蓣皂苷对肝细胞活力有明显的抑制作用,IC50为2.25μg/ml;②10μg/ml的薯蓣皂苷能升高肝细胞上清中的AST、ALP、LDH,2.5和5μg/ml的薯蓣皂苷能升高肝细胞上清中的ALP,随着薯蓣皂苷浓度剂量的增加,肝细胞不同程度的减少、变圆、甚至死亡;③5和10μg/ml的薯蓣皂苷能使肝细胞不同程度的出现凋亡和坏死的现象;④整体实验表明,给药组每日从尾静脉给予薯蓣皂苷10mg/kg连续7天,小鼠血清中的AST和LDH水平出现升高,仅有1只小鼠肝脏出现肝细胞广泛水肿和2只小鼠出现偶见巨核肝细胞现象。结论:大剂量的薯蓣皂苷可能对肝脏具有一定的毒性。To test the hepatotoxicity of Dioscin through In vitro experiments. Methods： ① MTTassay was used to test the cell viabili- ty. ②The contents of AST, ALP, LDH in hepatocytes supernatant were detected and morphological changes of hepatocytes were observed through inverted phase contrast microscope. ③ell apeptosis and necrosis were detected through Hoechst-PI staining method. ④fter giving 10 mg/kg Dioscin by intravenous administration to mice for 7 days ,the influence of hepatic function and histopathology in mice was investiga- ted. Results： ①he MTTassay showed that Dioscin could inhibit L-02 cells viability obviously and IC50 is about 2.25p, g/ml. ②10μg/ml Dioscin could increase the contents of AST, ALP, LDH while 2.5 and 5p.g/ml Dioscin could increase the contents of ALP in hepatocytes su- pernatant（ P 〈 0.01 or 0.05 ）. Cell morphology showed that Dioscin could damage the shapes of hepetocytes in a dose-dependent manner. ③5 and 10p,g/ml Dioscin could cause cell apeptosis and necrosis. ④he animal experiment showed that LDH and AST in blood serum were increased（ P 〈0.05 or 0.01 ）o Histopathological examination revealed that only one mousesliver had widespread hepatocyte edema and two had magnocellular nucleus of liver ceils. Conclusion： Dioscin may cause hepatotoxicity.

关 键 词：薯蓣皂苷 肝细胞 肝毒性 

分 类 号：R285[医药卫生—中药学]