氢化可的松诱导的肾阳虚大鼠尿液代谢组学研究

Urinary Metabonomic Study of Kidney-yang Deficiency Syndrome Induced by Hydrocortisone

目的:运用代谢组学方法研究氢化可的松诱导的肾阳虚大鼠尿液代谢表型的经时轨迹变化,鉴定与肾阳虚相关的代谢标志物来探讨肾阳虚相关代谢途径。方法:利用核磁共振氢谱(1H-NMR)技术建立大鼠尿液的代谢指纹谱,应用主成分分析和正交偏最小二乘判别分析研究肾阳虚大鼠尿液代谢表型的经时轨迹变化,应用正交偏最小二乘判别分析研究对照组和模型组之间的代谢物谱差异,并通过变量重要性投影(VIP)在尿液中选取生物标志物。结果:氢化可的松诱导的肾阳虚大鼠尿液代谢表型呈现明显的轨迹变化,在尿液中鉴定了与肾阳虚相关的13种生物标志物。肾阳虚大鼠机体能量代谢紊乱、肠道菌群受到扰动、甲基转移反应被抑制、氨转运功能受阻,同时,伴随一定程度的肾损伤。结论:该研究为探讨肾阳虚证的发生、发展及其病理机制、诊断的客观化和补肾阳中药的药效评价提供了一种新方法。

Objective：To investigate the time-dependent metabolic profiles of hydrocortisone-induced Kidney-yang deficiency syndrome in rats and to identify the corresponding potential biomarkers.Method：Proton nuclear magnetic resonance（1H-NMR） technique was used to analyze the rat metabonome in urine.Principal components analysis（PCA） and orthogonal partial least squares discriminant analysis（OPLS-DA） were processed to analyze the time trajectories of urinary metabonome in rats with ＇Kidney-yang deficiency syndrome＇.OPLS-DA was employed to study the metabonome difference between the control and hydrocortisone treated samples.Potential biomarkers were selected via the parameter of variable importance in the projection（VIP）.Result：Time trajectories of urinary metabonome of hydrocortisone-treated rats were drawn.Thirteen potential biomarkers were selected in rat urine.Conclusion：After hydrocortisone treatment,the energy metabolism and gut microflora environment were seriously disturbed,and transmethylation and transportation of amine were surpressed,in combination with kidney impairment.The results obtained suggested that metabonomic studies could be treated as a potential powerful approach in investigation of the onset and progression of ＇Kidney-yang deficiency syndrome＇,the pathological mechanism studies,objective diagnosis and the evaluation of traditional Chinese medicines that can replenish the kidney.