Huang Tzu-Chuan, Chen Shih-Ming, Li Yi-Chieh, Lee Jen-Ai
School of Pharmacy, College of Pharmacy, Taipei Medical University, No. 250, Wuxing St, Taipei 11031, Taiwan.
Biomed Chromatogr. 2013 Sep;27(9):1100-6. doi: 10.1002/bmc.2908. Epub 2013 Apr 3.
Urinary d-lactate is highly correlated to diabetic nephropathy - a progressive kidney disease in renal glomeruli. In this study, we used a C3H/3e mouse model to investigate the relationship between urinary d-lactate and aristolochic acid nephropathy where the glomerular structure is not affected. The nephropathy was induced using intravenous injections of aristolochic acid at a dosage of 10 mg/kg per day for 5 days and was characterized biochemically and histologically. The urinary excretions of proteins, N-acetyl-β-d-glucosaminidase and serum creatinine were determined and connected to histological conventional findings. Urinary d-lactate was analyzed using column-switching high-performance liquid chromatography with fluorescence detection. The results showed a remarkable increase of urinary markers, including of urinary proteins and N-acetyl-β-d-glucosaminidase, and the histological examination confirmed a diagnosis of acute tubule necrosis. The ratio of d-lactate to creatinine in the urine of aristolochic acid-treated mice was approximately 36 times greater than that of the mice in the control group (p < 0.05). The ratios for the two groups of mice were 311.00 ± 71.70 and 8.60 ± 1.80 µmol/mmol creatinine, respectively. These data confirm in vivo that urinary d-lactate reflects renal injury conditions in aristolochic acid-treated mice and may be a marker for the assessment of nephropathy.
尿d-乳酸与糖尿病肾病高度相关，糖尿病肾病是一种发生于肾小球的进行性肾脏疾病。在本研究中，我们使用C3H/3e小鼠模型来研究尿d-乳酸与马兜铃酸肾病之间的关系，马兜铃酸肾病中肾小球结构未受影响。通过每天静脉注射剂量为10 mg/kg的马兜铃酸，持续5天来诱导肾病，并对其进行生化和组织学特征分析。测定尿蛋白、N-乙酰-β-d-氨基葡萄糖苷酶和血清肌酐的尿排泄量，并将其与组织学常规检查结果相关联。使用柱切换高效液相色谱法和荧光检测法分析尿d-乳酸。结果显示，包括尿蛋白和N-乙酰-β-d-氨基葡萄糖苷酶在内的尿标志物显著增加，组织学检查确诊为急性肾小管坏死。马兜铃酸处理组小鼠尿液中d-乳酸与肌酐的比值约为对照组小鼠的36倍（p < 0.05）。两组小鼠的比值分别为311.00±71.70和8.60±1.80 μmol/mmol肌酐。这些数据在体内证实，尿d-乳酸反映了马兜铃酸处理组小鼠的肾损伤情况，可能是肾病评估的一个标志物。
