基于^1H—NMR的代谢组学方法对醋制甘遂解毒作用的研究

^1H-NMR based metabonomic approach to evaluate detoxification effect of vinegar-processed Euphorbia kansui

甘遂为有毒中药,临床上常经醋制后入药以降低其毒性。该文采用代谢组学方法比较生甘遂和醋甘遂对正常大鼠的损伤情况,研究醋制对甘遂毒性的缓解作用。连续7 d以生甘遂(EK)、醋甘遂(VEK)的水提取物对大鼠灌胃给药,药量均为9 g·kg-1·d-1(按生药量计),对照组给予生理盐水。停止灌胃后继续观察7 d,收集14 d白天尿液,用于1H-NMR检测;于第8天将每组大鼠处死一半,第15天处死另一半,采集肝脏,一部分用于1H-NMR检测,另一部分用于病理学切片检测。病理学切片检测结果显示在本实验剂量下甘遂及醋制甘遂对大鼠肝脏没有造成损伤,但代谢组学方法分析发现在实验的第2周甘遂造成大鼠肝、肾及消化系统内部内源性代谢产物谱的紊乱;同时发现醋甘遂的毒性要比生甘遂低得多,传统醋制可以降低甘遂的毒性。该研究显示代谢组学方法有助于评价甘遂的毒性及醋制对甘遂的解毒作用。

Euphorbia kansui （EK） is a toxic herbal drug, and often used after vinegar-processing to reduce its toxicity. In present study, a ^1H-NMR based metabonomic approach was used to evaluate the detoxification effect of vinegar-processed EK. The wa- ter extracts of EK and VEK were administered orally to male SD rats at doses of 9 g · kg^-1· d^-1 for 1 week, respectively, and one more week observation was further conducted. The control group was orally given with saline. Histopathological studies of liver samples on the 8^th and 15^th day were conducted, and the metabolites of rat urine and liver were analysed by ^1H-NMR. Histopathological studies of liver samples from EK and VEK treated rats showed no negative impacts. In metabonomic analyses of urines, changes of metabolites indicated liver damages, kidney lesions and imbalance of gut microbes in the second week. VEK-treated rats showed a quite lower tox- icity compared with EK-treated ones. The present study revealed that the metabonomic approach might be helpful for the evaluation of toxicity of EK and detoxic effect of VEK.