藜麦皂苷灌胃后大鼠尿液代谢及肠道菌变化

Changes of Urine Metabolism and Gut Microbiome in Rats after Intragastric Administration of Quinoa Saponins

以藜麦皂苷为材料,对成年健康Sprague Dawley大鼠进行90 d经口暴露后结合肠道菌群及尿液代谢组学研究,探究其对肾脏的影响。实验分别将雌雄大鼠(n=48)分为高剂量(500 mg/kg)皂苷灌胃组、中剂量(50 mg/kg)皂苷灌胃组、低剂量(5 mg/kg)皂苷灌胃组与空白对照组,经口灌胃处理后,对肠道内容物进行16S rDNA分析,对尿液代谢物采用UPLC-MS分析,探究皂苷对大鼠的肠道菌群及代谢组学的影响。在雌雄大鼠中高剂量组大鼠肾脏切片均发生部分炎性变化。代谢组学结果显示,中低剂量组与空白对照组相比无明显差异,高剂量组大鼠在藜麦皂苷灌胃后,雌性大鼠尿液中发现差异代谢物101种,雄性大鼠尿液中发现差异代谢物29种,影响了维生素B6代谢、氨循环、色氨酸代谢等代谢过程。肠道菌群分析显示,藜麦皂苷灌胃组与对照组大鼠肠道菌群多样性差异明显。综上所述,藜麦皂苷在低剂量下无明显的毒性反应,然而在不可接触的中高剂量下有潜在的肾毒性。

The saponins from Chenopodium quinoa were used as the material for 90-day oral exposure to healthy adult Sprague Dawley rats to evaluate the effects of the saponins on rats’ kidneys in combination of gut microbiome with urine metabolomics studies. Rats(n = 48, half male and female) were divided into the high-dose(500 mg/kg saponin) treatment group, medium-dose(50 mg/kg saponin) treatment group,low-dose(5 mg/kg saponin) treatment group and blank control group. After oral gavage, the intestinal fluids were collected from the rats for examining the effects of saponins on intestinal flora by 16S rDNA, and analyzing rats’ urine metabolomics by UPLC-MS. Partial inflammatory changes were observed in the kidney slices of male and female rats in both the medium-and high-dose groups. The results of metabolomics showed that there was insignificant difference between the medium-and low-dose groups. 101 kinds of differential metabolites were found in the urine of female rats while 29 kinds of differential metabolites were found in the urine of male rats after administration of the high dose of quinoa saponins, with metabolic processes such as vitamin B6 metabolism, ammonia cycle and tryptophan metabolism being affected. The gut microbiome analysis revealed the significant differences in the diversity of gut microbiome between the treatment group and the control. In summary, quinoa saponins at a low dose had insignificant toxicity, but exhibited potential non-contact nephrotoxicity at medium-high doses.