草乌致大鼠肝肾亚急性毒性的代谢组学研究

Metabonomic study on the subacute toxicity of liver and kidney induced by Aconiti Kusnezoffii Radix in rats

目的基于代谢组学技术分析和探讨草乌致大鼠肝肾亚急性毒性的生物标志物和可能的作用机制。方法以草乌为示例药物,以大鼠为研究对象,除正常组外,给药组灌胃相应溶液,连续给予28 d。通过代谢组学技术对采集的大鼠血清、肝、肾样本进行检测,用主成分分析结合偏最小二乘判别分析筛选肝肾亚急性毒性敏感标志物及代谢通路。结果代谢组学分析显示,与正常组比较,草乌组血清、肝、肾样本中分别鉴定得到34、23和30个差异代谢物,主要富集于ABC转运蛋白、精氨酸和脯氨酸代谢、癌症的中心碳代谢、烟酸和烟酰胺代谢等通路。结论初步认为草乌通过影响ABC转运蛋白、精氨酸和脯氨酸代谢、癌症的中心碳代谢等对肝肾造成损伤,亚精胺、羟脯氨酸、葡萄糖、L-亮氨酸和尿素可作为潜在的肝肾毒性敏感生物标志物。

Objective To analyze and discuss the biomarkers and possible mechanisms of subacute toxicity of liver and kidney induced by Aconiti Kusnezoffii Radix in rats based on metabonomics technology.Methods Taking Aconiti Kusnezoffi Radix as the target drug and SD rats as the research objects,each administration group except the normal group of the corresponding drug solution were gavaged for 28 days.The collected serum,liver and kidney samples of the rats were tested by metabonomics technology.The principal component analysis(PCA)combined with partial least squares discriminant analysis(PLS-DA)was used to screen sensitive markers and metabolic pathways of subacute toxicity of liver and kidney.Results Metabolomics analysis showed that compared with the normal group,34,23 and 30 differential metabolites were identified respectively in the serum,liver and kidney samples of Aconiti Kusnezoffii Radix group,which were mainly enriched in ABC transporters,arginine and proline metabolism,central carbon metabolism in cancer,nicotinate and nicotinamide metabolism etc.pathways.Conclusion It is preliminarily suggested that Aconiti Kusnezoffii Radix causes damage the liver and kidney by affecting the metabolism of ABC transporters,arginine and proline metabolism,central carbon metabolism in cancer,and that spermidine,hydroxyproline,glucose,L-leucine and urea can be used as potential hepatotrenetoxic sensitive biomarkers.