将NMR谱和主成分分析(principal component analysis,PCA)相结合用于研究不同剂量下乌头碱(aconitine,AC)急性毒性作用后大鼠尿样的代谢特征.结果表明灌胃给药后代表能量代谢的柠檬酸(citrate),2-酮戊二酸(2-oxoglutarate)和顺乌火酸(cis—aconitate),反应肠道菌群代谢状况的马尿酸盐(hippurate)和苯乙尿酸(phenylacetylglycine)出现异常,并且这些变化在给药后O~8h达到最大,16h后基本恢复正常.且给药剂量越大代谢物异常越明显,需要的恢复时间也越长.实验中发现2-oxoglutarate的异常增加可能与AC的神经毒性有关,或与2-oxoglutarate的代谢异常有关.这些信息为进一步阐明AC的毒理学机制和临床毒性监测都会有一定的帮助.
^1H NMR spectroscopy and principal component analysis (PCA) were used to characterize the urinary metabolic profiles of rats treated with aconitine (AC). Compared to the control animals, the rats treated with AC showed increased levels of citrate, 2-oxoglutarate and cis-aconitate, and decreased levels of hippurate and phenylacetylglycine in the urine. Such metabolic changes may have reflected, respectively, the changes in body energy metabolism and in the metabolism of intestinal flora in response to AC treatment. Increase of the 2-oxoglutarate level may have also indicated the neurotoxic effects of AC. The results also showed that the changes in urinary metabolic profiles induced by AC were time- and dosage-dependent, being the most prominent between 0-8 hrs post-treatment, returning gradually towards the control level between 8 -16 hrs post-treatment in the low-dose group, but not in the high-dose group. The results obtained in this study may be useful for understanding the toxicological effects of AC.