中药柴胡总皂苷急性肝毒性的代谢组学研究

Metabolomics on acute liver toxicity of saikosaponin in Chinese medicine bupleuri radix

运用UPLC-MS联用技术对空白对照组、柴胡总皂苷(SS)组大鼠在给药后第3天和第5天的尿液样本进行分析检测,获得了以质荷比和保留时间为变量的矩阵数据。据此建立各组大鼠的尿液代谢轮廓图,并利用主成分分析(PCA)建立了SS的代谢组学毒性模型。结合肝组织病理,探讨了柴胡总皂苷的急性肝毒性。对于SS组与正常组,大鼠尿液代谢轮廓图表现出了一定的差异。在代谢组学毒性模型中,给药第3天和第5天的PCA分类均偏离正常组,而第5天的偏离程度强于第3天。同时,在第5天的肝组织病理切片中发现了组织病变。由此表明,给药组大鼠的代谢组偏离了正常组,这种偏离正是肝急性毒性的表现,且给药到第5天的肝毒性强于第3天,表明肝毒性与给药累积剂量呈正相关,表现出了明显的急性和累积肝毒性。

The rats＇ urine samples,which were collected in the third and fifth day after giving drug,were detected by using the UP- LC-MS technology. The used rats were divided into control group and saikosaponin group（ i. e SS one）. The measured data matrix u- sing mass-to-charge ratio and retention time as variables were acquired. By using the matrix, the rats＇urine metabolic profiles were obtained. The SS metabonomics toxic models for liver had been established by using principal component analysis （PCA）. The acute liver toxicity of saikosaponin had been studied based on the established models combined with the liver pathological section. The differences of the rats＇ urine metabolic profiles were found between the SS group and the normal group. In the metabonomics toxic model,PCA classes of day 3 and day 5 all were away from the class of the normal group, and the departure degree of day 5 was stronger than day 3. At the same time, organization lesions were found in the liver pathological section of day 5. Liver acute toxicity of saikosaponin could be expressed based on the departure SS metabolic group from the normal group in the metabonomics toxic model. Since the toxicity in day 5 after giving drug was stronger than day 3, the liver toxicity was positively related to cumulative dose of the given drug. It was shown that there was obvious acute liver toxicity and accumulated one for saikosaponin.