柴胡总皂苷粗提物致大鼠肝毒性及氧化损伤机制相关性研究

Study on Hepatotoxicity on rats caused by crude extracts of total saikosaponins and correlation with oxidative damage mechanism

目的:观察长期、大量给予柴胡总皂苷粗提物导致大鼠肝毒性损伤程度及与氧化损伤机制的相关性。方法:按45 d毒性试验方法,给大鼠灌胃柴胡总皂苷粗提物,按柴胡总皂苷计算,高、中、低剂量组分别为100,50,10 mg.kg-1,45 d后观察一般状况,检测肝功能相关指标,检测血和肝组织内脂质代谢情况、糖代谢、胆红素(TBIL)水平和肝组织病理检查;检测血中总巯基(-SH)的量和血、肝组织内丙二醛(MDA)水平、超氧化物歧化酶(SOD)活性、谷胱甘肽(GSH)和谷胱甘肽过氧化物酶(GSH-Px)的量和活性。结果:柴胡总皂苷粗提物可导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,肝脏重量和肝体比值增大,血和肝内TG含量增加,对血中胆固醇(CHO)和肝内糖原(Gn)影响不明显,仅高剂量组对TBIL有影响;病理组织学检查可见肝细胞损伤。可导致血中总-SH的量增加;血和肝内MDA水平、GSH含量增加,SOD,GSH-Px活性下降。上述变化随剂量的增加而逐渐加重,与蒸馏水对照组比较有明显差异。结论:柴胡总皂苷粗提物可导致大鼠明显的肝毒性损伤,其损伤途径与氧化损伤机制有关。

Objective： To observe the degree of hepatotoxicity damage to rats and the correlation with oxidative damage mechanism after taking a large dose of crude extracts of total saikosaponins for a long time.Method： According to 45-day toxicity experimental methods,rats were successively administrated with crude extracts of total saikosaponins.High,middle and low dose were respectively 100,50,10 mg·kg-1 calculated by total saikosaponins.The general conditions were observed and the related index of liver function,the metabolism condition of lipids,the glycometabolism,the level of TBIL were determined and the histopathologic examination of hepatic tissue were examined.The content of total-SH in serum,the level of MDA,the activity of SOD and the content and activity of GSH and GSH-Px in serum and liver tissue were detected.Result： The crude extracts of total saikosaponins can increase the activity of ALT and AST in blood,increase liver weight and the ratio of liver to body,increase the content of TG in blood and liver.The effect on CHO in blood and Gn in liver is not obvious.Only high dose group′s effect on TBIL can be observed.The hepatic cell damage is obvious in the histopathologic examination of hepatic tissue.The crude extracts of total saikosaponins can increase the content of total SH in blood,the content of MDA and GSH in blood and liver,while decrease the activity of SOD and GSH-Px in blood and liver.The above-mentioned changes gradually aggravates with dose increasing,and is obvious compared with distilled water control group.Conclusion： The crude extracts of total saikosaponinscan induce hepatotoxicity damage,and the mechanism of hepatic damage is related with oxidative damage mechanism.