柴胡总皂苷对小鼠肝毒性“量-时-毒”关系研究

目的:研究柴胡总皂苷醇洗脱物(81.9%)单次给药致小鼠肝毒性的时毒、量毒关系。方法:取小鼠按不同时间点和不同剂量分组,观察小鼠死亡情况和毒性反应,检查血清谷丙转氨酶(ALT)、谷草转氨酶(AST),计算肝、脾、胸腺脏器指数,光学显微镜下观察肝组织形态变化。结果:时-毒关系研究表明:按柴胡总皂苷含量计算,小鼠单次灌服74.5 mg/kg的柴胡总皂苷醇洗脱物后,小鼠血清ALT、AST均在给药后1～2 h达到高峰,48 h开始恢复,72h恢复近正常值;肝组织病理形态学检查显示柴胡总皂苷醇洗脱物给药8～24 h后可对肝组织产生明显损伤。量-毒关系研究表明:与正常组比较,柴胡总皂苷醇洗脱物不同剂量组(按柴胡总皂苷含量计算,分别为74.5,59.6,47.7,38.2,30.6,24.5 mg/kg)对肝组织产生不同程度的损伤,且随着剂量增大,ALT、AST升高显著,呈剂量依赖关系;肝组织病理形态学检查显示柴胡总皂苷醇洗脱物不同剂量组小鼠肝组织出现不同程度的肝细胞水肿和脂肪变性,其中高剂量组甚至出现片状坏死、小叶结构不清。结论:小鼠单次灌胃等生药量不等总皂苷含量的柴胡总皂苷醇洗脱物造成的急性肝损伤明显重于粗品,并呈现一定的时毒、量毒关系。

Study on dose-time-toxicity relationship on hepatotoxicity in mice caused by alcohol elution of Bupleurum Saikosaponin

Objective: To study the time-toxicity and dose-toxicity relationships caused by alcohol elution of Bupleurum saikosaponin(81.9%) to mice.Methods: Mice were packeted according to different time and dose points,to observe the death circumstance and toxicity of mice,detect ALT 、AST in serum,calculate liver,spleen,thymus index,and observe the of liver tissue under light microscope.Results: The time-toxicity relationship showed that: caculated by the content of total saikosaponin,ALT,AST in mice serum administrated to 74.5 mg/kg alcohol elution of Bupleurum saikosaponin were peaked after 1～2 hours’ administration,began to restore in 48 hours and restore to near normality in 72 hours,and the pathological examination of hepatic tissue showed that the refined products of Bupleurum saikosaponin with alcohol elution after 8～24 hours’ administration to mice could produce significant liver damage.The dose-toxicity relationship showed that:compared with the normal group,the different dose refined products of Bupleurum saikosaponin with alcohol elution(caculated by the content of total saikosaponin,the dosage was separately 74.5,59.6,47.7,38.2,30.6,24.5 mg/kg) could produce different degree’s damage to hepatic tissue,the ALT,AST in serum increased significantly with the dose increased and had dose-dependence ralationship.The pathological examination of hepatic tissue showed that under light microscope,the different doses’ liver tissue of mice all had different degree’s edema and fatty degeneration in liver cells,and the high-dose group appeared to be necrosis,lobular structure unclear.Conclusion: The acute liver injury caused by single dose refined products of Bupleurum saikosaponin with alcohol elution to mice was more serious than the total Bupleurum saikosaponin extracts,and there were certain time-toxicity and dose-toxicity relationships.