The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen Univ., Xiamen 361005, China.
Am J Physiol Renal Physiol. 2011 Apr;300(4):F947-56. doi: 10.1152/ajprenal.00551.2010. Epub 2011 Jan 12.
Elucidation of the metabolic profiling in diabetic nephropathy (DN) rats is of great assistance for understanding the pathogenesis of DN. In this study, ¹H-nuclear magnetic resonance (NMR)-based metabonomics combined with HPLC measurements was used to quantitatively analyze the metabolic changes in urine and kidney extracts from diabetic 2-wk and 8-wk rats induced by streptozotocin (STZ). Pattern recognition analysis of either urine or kidney extracts indicated that the two diabetic groups were separated obviously from the control group, suggesting that the metabolic profiles of the diabetic groups were markedly different from the control. The diabetic 8-wk rats showed lower levels of creatine, dimethylamine, and higher levels of ascorbate, succinate, lactate, citrate, allantoin, 2-ketoglutarate, and 3-hydrobutyrate (3-HB) in the urine samples. Moreover, the diabetic 8-wk rats displayed lower levels of succinate, creatine, myo-inositol, alanine, lactate, and ATP, and higher levels of 3-HB and glucose in the kidney extracts. The observed metabolic changes imply the enhanced pathways of either lipid or ketone body synthesis and decreased pathways of either tricarboxylic acid cycle or glycolysis in DN rats compared with the control. Our results suggest that the energy metabolic changes are associated with the pathogenic process of DN.
阐明糖尿病肾病（DN）大鼠的代谢特征对于了解 DN 的发病机制具有重要意义。在这项研究中，采用基于 ¹H-核磁共振（NMR）的代谢组学结合 HPLC 测量方法，定量分析了链脲佐菌素（STZ）诱导的 2 周和 8 周糖尿病大鼠尿液和肾提取物中的代谢变化。无论是尿液还是肾提取物的模式识别分析都表明，两个糖尿病组与对照组明显分开，表明糖尿病组的代谢谱与对照组明显不同。糖尿病 8 周大鼠的尿液样本中肌酸、二甲胺水平降低，抗坏血酸、琥珀酸、乳酸、柠檬酸、尿囊素、2-酮戊二酸和 3-羟丁酸（3-HB）水平升高。此外，糖尿病 8 周大鼠的肾提取物中琥珀酸、肌酸、肌醇、丙氨酸、乳酸和 ATP 水平降低，3-HB 和葡萄糖水平升高。观察到的代谢变化表明，与对照组相比，DN 大鼠的脂质或酮体合成途径增强，三羧酸循环或糖酵解途径减弱。我们的结果表明，能量代谢变化与 DN 的发病过程有关。
