山豆根不同组分多次给药对小鼠肝毒性"量-时-毒"关系研究

目的 研究山豆根不同组分多次给药致小鼠肝毒性的"量-时-毒"关系.方法 连续7天给小鼠灌胃不同剂量的山豆根水提、醇提组分,观察小鼠一般状况,分别于给药后第1、3、7天检测小鼠血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(AKP)的活性和总胆红素(TBI)、白蛋白(ALB)的含量,计算肝脏指数,并观察肝组织形态变化.结果 在给药后第1天山豆根水提、醇提组分低剂量组未对小鼠肝脏造成明显损伤,高、中剂量组会使小鼠血清中ALT、AST、AKP活性升高,TBI含量升高,ALB含量下降;给药后第3天山豆根水提、醇提各剂量组小鼠出现烦躁,体重增长缓慢等症状,血清中上述肝功能指标变化明显,肝体比值增大,并见部分肝细胞脂肪变性、气球样变,点状坏死等病理变化;给药后第7天观察上述症状依次加重.水提组分对上述指标的影响比醇提组分明显.结论 多次给小鼠高、中剂量的山豆根水提组分和醇提组分均可造成明显的肝损伤,且水提组分的肝毒性大于醇提组分,并呈现明显的肝毒性"量-时-毒"关系.

Experimental Study on the "Dose-Time-Toxicity" Relationship of Hepatotoxicity Induced by Different Components from Radix et Rhizoma Sophorae Tonkinensise in Mice

Objective The ＂dosage-time-toxicity＂ relationship of hepatotoxicity induced by multiple administration of water extract and alcohol extract of Radix et Rhizoma Sophorae Tonkinensise to mice was studied.Methods Mice are divided into different groups such as normal group,water extract group and alcohol extract group,and the normal conditions were observed after seven days administrated.And the activity of ALT、AST、AKP、TBI、ALB in serum,the liver weight and volume ratio,the changes of liver morphology was observed separately on the d1、d3、d7 after administration.Results The rat＇s body weight was effected,both the activity of ALT、AST、AKP in serum and TBI were increased,while the ALB was decreased,the liver weight and volume ratio was increased,and the liver pathology tissue changed after given water extract and alcohol extract from Radix et Rhizoma Sophorae Tonkinensise to mice by intragastric for 7 days.These changes were reduced on the 3th day after ig and on the 1th day after ig,thesechanges with the high,medium dosage were reduced again,but the low dosage didn＇t have these phenomenon especially the water extract.Conclusion Multiple intragastric administrations of water extract and alcohol extract of Radix et Rhizoma Sophorae Tonkinensise with certain dosage may induce acute hepatotoxical injury in mice especially the water extract and this show an obvious ＂dosage-time-toxicity＂ relationship.