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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。
Objective: To study the relationship between “quantity - time - toxicity” of multiple toxic effects of volatile oil of Bupleurum chinense on rat liver. Methods: The volatile oil of Bupleurum chinense was administered into the Wistar rats for 30 consecutive days. The levels of ALT and AST, the ratio of hepatic cells and the histopathological changes of the rats were detected on the days 71, 52, Results: The volatile oil from Radix Bupleurum was administered intragastrically (0.19 ~ 0.42) ml / kg for 30 days, which could induce hepatotoxicity in rats. The hepatotoxicity could be induced within 7 days after treatment. The serum ALT and AST activities were significantly increased in all dose groups, Hepatic body ratio increased (0.26 ~ 0.42) ml / kg group showed slight pathological liver injury. The hepatotoxicity was the most obvious in 15-21 days after treatment, and the activity of ALT and AST in serum was significantly increased. Compared with the blank group, all the dose groups showed significant difference in varying degrees, Significantly increased; liver pathological damage. 30 days after the drug, rats died, ALT, AST activity and liver ratio increased 21 days compared to no significant. CONCLUSION: The dose of volatile oil from Bupleurum chinense L. induced by hepatic toxicity is (0.19 ~ 0.42) ml / kg, equivalent to 92.6 ~ 204.7 g / kg of crude drug, equivalent to 70kg per day (1.5 ~ 3.4) times.