商陆致大鼠肾损伤的代谢组学研究

Study on metabonomics of kidney injury of rats caused by pokeberry root

目的:通过代谢组学研究大鼠给予商陆后尿液代谢产物的变化,探讨商陆肾损伤机制。方法:大鼠随机分为商陆组和对照组,每天灌胃给予20g/kg商陆或纯水,连续49d。采用气相色谱-质谱联用(GC-MS)检测20、48d尿液中代谢产物变化。结果:给药20d后,商陆组与对照组大鼠的尿液代谢谱明显分开。与对照组比较,商陆可引起尿液中α-酮戊二酸、柠檬酸、苹果酸等显著上升,而异亮氨酸、肌酐、甘氨酸等则显著降低。其中α-酮戊二酸等产物的上升提示商陆可能通过三羧酸循环的紊乱,引起线粒体、细胞凋亡。甘氨酸的降低可能与氧化应激相关。结论:大剂量商陆可引起大鼠体内代谢产物的明显变化,其肾损伤机制可能是通过影响三羧酸循环、氨基酸代谢等通路,进而引起氧化应激反应及细胞凋亡的发生。

Objective： To investigate the mechanism of renal injury caused by pokeberry root（PR） through observing changes of urinary metabolites of rats received gavage administration with PR decoction by using metabolomic method. Methods： Rats were randomly divided into control and PR groups, and rats in the two groups received gavage administration with pure water or 20g/kg PR respectively for 49 days. Urine was collected on the 20 th and 48 th day respectively and the changes of urinary metabolites were detected by using GC-MS. Results： The urine spectrum of rats in RP and control groups on the 20 th day was separated clearly. Compared with control group, the concentrations of α-ketoglutaric acid, citric acid and malic acid of rats in PR group were increased significantly, while the concentrations of isoleucine, creatinine and glycine were decreased significantly. The increase of α-ketoglutaric acid, citric acid concentrations indicated that PR might cause the apoptosis of mitochodria and cells by causing the disorder of tricarboxylic acid cycle, and the decreasing of glycine concentrations might relate with the oxidative stress. Conclusion： Large dose of PR can cause remarkable changes in metabolites in rat bodies. The mechanism of renal injury caused by PR might relate to the influence on pathways of tricarboxylic acid cycle and amino acid metabolism, and then inducing the occurrence of oxidative stress and cell apoptosis.