Joint Bioanalytical Research Team, Korea Basic Science Institute, Seoul, Korea.
Am J Physiol Renal Physiol. 2010 Feb;298(2):F461-70. doi: 10.1152/ajprenal.00389.2009. Epub 2009 Nov 18.
Lithium (Li) treatment for bipolar affective disorders is associated with a variety of renal side effects. The metabolic response of the kidney to chronic Li treatment has rarely been studied. We applied a novel method of (1)H-nuclear magnetic resonance (NMR)-based metabonomics to integrate metabolic profiling and to identify the changes in the levels of metabolites in the kidney and urine from rats with Li-induced NDI. Metabolic profiles of urine and kidney homogenate [3 different zones (cortex, outer medulla, and inner medulla) or whole kidney] were investigated using high-resolution NMR spectroscopy coupled with pattern recognition methods. The accurate concentrations of metabolites in kidney homogenates and urine were rapidly measured using the target-profiling procedure, and the difference in the levels of metabolites was compared using multivariate analysis, such as principal component analysis and orthogonal partial least squares-discriminant analysis. Major endogenous metabolites for kidney homogenates contained products of glycolysis (glucose, lactate) and amino acids, as well as organic osmolytes (e.g., betaine, myo-inositol, taurine, and glycerophosphocholine). Many metabolites revealed changes in their levels, including decreased levels of organic osmolytes and amino acids in the inner medulla. A number of urinary metabolites were changed in Li-induced NDI, and in particular, elevated urinary levels of acetate, lactate, allantoin, trimethylamine, and creatine could suggest Li-induced renal cell stress or injury. Taken together, metabonomics of kidney tissue and urine based on (1)H-NMR spectroscopy could provide insight into the effects of Li-induced renal effects and cell injury.
锂（Li）治疗双相情感障碍与多种肾脏副作用有关。肾脏对慢性 Li 治疗的代谢反应很少被研究。我们应用了一种新的（1）H-核磁共振（NMR）基于代谢组学的方法，整合代谢谱分析，以鉴定 Li 诱导的 NDI 大鼠肾脏中代谢物水平的变化。使用高分辨率 NMR 光谱结合模式识别方法研究了尿液和肾匀浆[3 个不同区域（皮质、外髓和内髓）或整个肾脏]的代谢谱。使用靶向分析程序快速测量肾匀浆和尿液中代谢物的准确浓度，并使用主成分分析和正交偏最小二乘判别分析等多变量分析方法比较代谢物水平的差异。肾匀浆中的主要内源性代谢物包含糖酵解（葡萄糖、乳酸）和氨基酸的产物，以及有机渗透物（如甜菜碱、肌醇、牛磺酸和甘油磷酸胆碱）。许多代谢物的水平发生了变化，包括内髓中有机渗透物和氨基酸水平的降低。Li 诱导的 NDI 导致许多尿液代谢物发生变化，特别是尿乙酸盐、乳酸盐、尿囊素、三甲胺和肌酸水平升高，可能提示 Li 诱导的肾细胞应激或损伤。总之，基于（1）H-NMR 光谱的肾组织和尿液代谢组学可以深入了解 Li 诱导的肾脏效应和细胞损伤的影响。
