北豆根不同组分多次给药对小鼠肝毒性“量-时-毒”关系研究

Experimental Study on the "Dose-time-toxicity" Relationship of Hepatotoxicity Induced by Different Components from Rhizoma Menispermi in Mice

目的研究北豆根不同组分多次给药对小鼠肝毒性"量-时-毒"关系的影响。方法小鼠按不同时间点或不同剂量分组,给小鼠灌胃北豆根水提和醇提组分,每天1次,连续灌胃7天,观察给药后小鼠死亡情况和毒性反应,分别于药后1、3、7天检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST),血浆清蛋白(ALB)、血清碱性磷酸酶(ALP)、胆红素(TBI)水平,并计算肝脏指数。结果北豆根水提组分和醇提组分可致血中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性增高,ALT、AST在给药后1天明显升高,以AST为更敏感,一直持续到7天。肝脏重量和肝体比值增大,血清碱性磷酸酶(ALP)、胆红素(TBI)水平增加,血浆清蛋白(ALB)降低;上述变化随给药次数和剂量的增加而逐渐加重,呈现一定的时间、剂量依赖性。结论小鼠多次灌胃给予一定剂量的北豆根水提组分或醇提组分可造成明显的肝毒性损伤,即肝功指标的改变,并呈现一定的"量-时-毒"关系。关于其肝脏损伤的机制有待进一步研究。

Objective To investigate the ＂dose-time-toxicity＂ relationship of hepatotoxicity caused by multiple dose water extracted and alcohol extracted components from Rhizoma Menispermi to mice. Methods Mice are grouped according to different time or dose points, the death condition and toxicity of mice were observed, the activity of ALT,AST,ALP,ALB,TBI in serum were detected, liver index was calculated. Results Compared with the control group, the level ofALT, AST, ALP, TBI in serum of water extracted and alcohol extracted components increased, how- ever the level of ALB reduced; and changes of the enzymatic activity in serum increased significantly with the dose increasing. Conclusion The continuous administration of different components from Rhizoma Menispermi to mice can induce obvious hepatotoxicity injury, and there were certain time-toxicity and dose-toxicity relationships.