痔血胶囊组方对原代培养大鼠肝细胞和小鼠肝脏的毒性  

Study on toxicity of medicinal ingredients of Zhixue capsule in primary rat hepatocytes and mice

作　　者：倪晓珺[1] 程能能[1] 

机构地区：[1]复旦大学药学院药理学教研室,上海201203

出　　处：《中国临床药学杂志》2010年第5期271-275,共5页Chinese Journal of Clinical Pharmacy

摘　　要：目的研究痔血胶囊组方白鲜皮和苦参对原代大鼠肝细胞和小鼠肝脏的毒性。方法二步灌流法分离原代大鼠肝细胞并接种于96孔板,培养贴壁后加入一系列浓度的苦参醇提物(ESF)、白鲜皮醇提物(ECD)、苦参白鲜皮复方醇提物(ECF)、苦参素及苦参碱,利用噻唑蓝(MTT)方法检测细胞存活率。另将30只小鼠随机分为溶剂对照组、潜在肝毒性组(50 mg·kg^(-1)),连续7 d尾静脉注射,测定血清丙氨酸氨基转移酶(ALT)和门冬氨酸氨基转移酶(AST)水平。结果体外实验中,孵育24 h后,苦参组250、500 mg·L^(-1)的肝细胞活力降至15%以下,与对照组相比活力显著降低(P<0.01)。ECD、ECF在质量浓度62.5～500 mg·L^(-1)内未见肝细胞活力抑制作用。苦参素(0.05～5 mol·L^(-1))、苦参碱(0.05～5 mol·L^(-1))对肝细胞活力均未见抑制作用。静脉注射7 d后,苦参组小鼠血清ALT水平与对照组相比显著升高(17.05 vs 12.81 U·L^(-1),P<0.05)。结论痔血胶囊的肝毒性很可能源于ESF。AIM To study the hepatotoxicity of Cortex dictamni and Radix sophorae flavescentis in rat primary hepatocytes and mice. METHODS Hepatocytes were isolated by the two-step perfusion and MTr method was used to evaluate the cell viability. Ethanolic extracts of Radix sophorae flavescentis （ESF）, Cortex dictamni（ECD） and compound formula （ECF）, matrine and oxymatrine were tested for their effects on cell viability. Hepatotoxic extracts were further administered intravenously to mice for 7 d, and liver injury was assessed by measuring the levels of aminotransferase （ALT） and aspartate aminotransferase （AST）. RESULTS Cell viability of hepatocytes treated with 250 and 500 nag＂ L- 1 ESF for 24 h were below 15 %, and significantly decreased compared with control group （ P 〈 0.01 ）. Hepatocytes were not injured by exposure to ECD or ECF ranged from 62.5 to 500 mg·L^-1. Matrine and oxymatrine did not affect cell viability at concentration range from 0.05 to 5 mol·L^-1. ESF also significantly increased the level of ALT in serum of mice administered with ESF 50 mg·kg^- 1 intravenously for 7 d （ 17.05 vs 12.81 U·L^-1, p 〈 0.05）. CONCLUSION The hepatotoxicity of Zhixue capsule could be mainly attributed to ESF.

关 键 词：痔血胶囊 肝毒性 原代肝细胞 谷氨酸氨基转移酶 

分 类 号：R285.5[医药卫生—中药学]