柴胡总皂苷肝毒性肝纤维化损伤机制研究

Study on the Hepatotoxicity Mechanism of Bupleurum Saikosaponin by Alcohol Elution on Hepatic Fibrosis

目的探讨柴胡总皂苷肝毒性损伤与肝脏纤维化的相关性,为阐明其肝毒性机制提供依据。方法大鼠连续15天灌胃高、中、低不同剂量,按等生药量计算,高、中、低剂量分别为300、150、50 mg.kg-1,末次药后取血和肝组织,检测血清及肝组织匀浆中羟脯氨酸含量的变化;并作大鼠肝脏组织Masson's病理学检查。结果 15天给药结束后药物组大鼠血清和肝组织羟脯氨酸含量均明显升高,随给药剂量增加羟脯氨酸含量升高幅度增大,与正常对照组比较呈现不同程度的显著性差异;马松染色肝组织病理改变可见胶原纤维延伸明显,并互相连接包绕整个肝小叶,导致正常肝小叶结构破坏,假小叶形成。药物高、中、低剂量之间的肝毒性损伤程度有一定的剂量依赖关系,与空白组相比有明显差异。结论连续15天灌服一定剂量的柴胡总皂苷可导致大鼠明显的肝纤维化,柴胡总皂苷是其肝毒性主要物质基础,为柴胡总皂苷的肝毒性评价提供了实验依据,为其毒性预警和临床安全应用提供对策及科学依据。

Objective To study the hepatotoxity mechanism of refined products from Bupleurum Saikosaponin by Alcohol Elution, and to discuss the relevance between hepatotoxcity and hepatic fibrosis, in order to provide the basis of hepatotoxity mechanism. Methods Refined products from Bupleurum Saikosaponin by alcohol elution of different dosages（ig） were given to Wistar rats for fifteen days consecutively. The changes of hydroxyproline in serum and liver tissue were detected and the histopathological study was performed. Results On the 15th day after ig the level of hydroxyprohne in serum and liver tissue increased obviously, which is in line with the dosages increased. Masson staining shows the pathological changes of hver collagen fiber extension is obvious, and connected to each other surrounding the hepatic lobule, leading group, the degree of hver to destruction of the normal lobular architecture, false lobule. Compared with the control damage has certain dependence on the dose. Conclusion Long-term administration of the refined products from Bupleurum Saikosaponin by alcohol elution with large doses can result in liver fibrosis in rats; the resuks of this study provide some experimental basis for the safe use of Bupleurum inchnical .The total Bupleurum saikosaponin was the main material basis of hepatoxicity.