柴胡挥发油大鼠肝毒性“量-时-毒”关系研究

Experimental study on the "dosage-time-toxicity" relationship of chronic hepatotoxicity induced by volatile oil from Bupleurum chinense in rats

目的:研究柴胡挥发油多次灌胃致大鼠肝毒性的"量-时-毒"关系。方法:连续30天给Wistar大鼠灌胃不同剂量的柴胡挥发油,分别于药后71、52、1、30天检测大鼠血清ALT、AST活性、肝体比值和病理组织学变化。结果:连续30天灌胃(0.19～0.42)ml/kg的柴胡挥发油可造成大鼠肝毒性损伤,药后7天即可产生明显肝毒性,各剂量组血清ALT、AST活性明显升高,肝体比值增大(,0.26～0.42)ml/kg组肝脏出现轻微病理损伤。药后15～21天肝毒性表现最明显,血清ALT、AST活性显著升高,与空白组比较,各剂量组均呈现不同程度的显著性差异,且随剂量增加升高更明显;肝体比值显著增大;肝脏病理损伤严重。药后30天,大鼠出现死亡,ALT、AST活性及肝体比值较21天增加不明显。结论:柴胡挥发油致大鼠肝毒性损伤的剂量范围是(0.19～0.42)ml/kg,相当于生药量(92.6～204.7)g/kg,按柴胡口服液计约相当于70kg人日用量的(1.5～3.4)倍。

To study the ＂dosage-time-toxicity＂relationship of hepatotoxicity induced by multiple intragastric administration of volatile oil from Bupleurum chinense.Methods：Volatile oil from Bupleurum chinense of different dosages was given to Wistar rats by intragastric administration for thirty days consecutively.The changes of the activity of ALT,AST and hepar index were detected and the histopathological study was performed.Results：Hepatotoxical injury in rats can be caused by intragastric administration of volatile oil from Bupleurum chinense for 30 days.On the 7th day after ig the hepatotoxicity which displayed with obvious increase of activity of serum ALT,AST and hepar index appeared.On the 15th～21th day the hepatotoxicity kept a higher level that the active units of serum ALT,AST were significantly higher than that of normal group.On the 7th day after ig the death increased obviously while the activity of serum ALT,AST and hepar index increased slightly.Conclusion：The dosage range of volatile oil from Bupleurum chinense to cause hepatotoxical injury in rats is（0.19～0.42）ml/kg,and it’s equivalent to（92.6～204.7）g/kg crude drug.This dosage is about（1.5～3.4）times of the clinical daily dosage of chaihu oral liquid.This study can offer reference to the monitor about toxical and side effect of the slather of preparation containing volatile oil from Bupleurum chinense for long time.It also has important significance on the safe and rational use of drugs in clinic.