柴胡总皂苷醇洗脱精制品对大鼠慢性肝毒性“量-毒”关系研究

"Dose-toxicity" relationship study on rat's chronic hepatoxicity of refined products of saikosaponin by alcohol elution

目的:观察连续15 d给予大鼠不同剂量的柴胡总皂苷醇洗脱精制样品导致大鼠肝毒性的损伤程度。方法:分别给予大鼠灌胃高、中、低剂量的柴胡总皂苷醇洗脱精制样品,按柴胡总皂苷计算,高、中、低剂量组分别为300,150,50 mg.kg-1,除观察一般状况外,检测血中肝功、肾功、脂质代谢、糖代谢相关指标;剖杀大鼠,精密称量心、肝、脾、肺、肾脏质量,计算脏体比值;进行肝脏病理组织学检查。结果:不同剂量的柴胡总皂苷醇洗脱精制样品可导致大鼠体重下降,导致血中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(AKP)、白蛋白(ALB)和总胆红素(TBI)水平增高,肝脏质量和肝体比值增大,病理学检查可见不同程度的肝组织损伤;上述变化随剂量的增加而逐渐加重,与空白组比较有明显差异。对尿素氮(BUN)、肌酐(Cr)、总蛋白(TPC)、胆固醇(CHO)、血糖(GLU)含量影响不明显。结论:柴胡对大鼠肝毒性损伤程度与柴胡用药剂量、柴胡总皂苷含量呈剂量依赖关系,并呈现一定的"量-毒"关系。柴胡总皂苷是柴胡导致肝毒性的毒效部位,柴胡总皂苷醇洗脱精制品(81.9%)在一定剂量下,连续给药15 d即可导致大鼠明显的肝脏器质性病变,其细胞损伤乃至坏死是主要病理改变。

Objective： To observe the degree of hepatoxicity damage to rats after taking different dose refined products of saikosaponin by alcohol elution for 15 days.Method： Caculated by total saikosaponins,the high,middle and low lose-group were respectively lavaged 300,150,50 mg·kg-1 refined products of saikosaponin by alcohol elution to rats.General state,the related index of hepatic function,renal function,the metabolism condition of lipids,the glycometabolism were all observed.After the rats dissected,the weight of heart,liver,spleen,lung,renal were precisely measured,and the ratio of organ to body was then calculated.The histopathologic of hepatic tissue was also examined.Result： Different dose refined products of saikosaponin by alcohol elution can induce the rats＇ body weight decreasing,the level of ALT,AST,AKP,ALB and TBI in serum increasing,the liver weight and the ratio of liver to body increasing.The hepatic tissue damage is obvious in the histopathologic examination of hepatic tissue.The above-mentioned indices gradually aggravate with dose increasin,and obviously different with distilled water control group.The influence on the content of BUN,Cr,TPC,CHO and GLU is not obvious.Conclusion： The degree of hepatoxicity damage caused by Bupleurum chinense has dose dependence with the dose of Bupleurum chinense and the content of saikosaponin,which showed some ＂dose-toxicity＂ relationship.The saikosaponin is mainly toxical component which induces the hepatoxicity.The refined products of saikosaponin by alcohol elution（81.9%） administrated continuously to rats for 15 days under the certain dose can significantly induce the organic lesions to rats＇ liver with the main pathological changes of cell damage and necrosis.