5/6 肾切除大鼠模型慢性肾脏病的组织、尿液和血液代谢物特征。
Tissue, urine and blood metabolite signatures of chronic kidney disease in the 5/6 nephrectomy rat model.
机构信息
Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajers Vej 7H, 9220, Aalborg, Denmark.
Department of Anaesthesia and Intensive Care Medicine, Aalborg University Hospital, 9000, Aalborg, Denmark.
出版信息
Metabolomics. 2019 Aug 17;15(8):112. doi: 10.1007/s11306-019-1569-3.
INTRODUCTION
Progressive chronic kidney disease (CKD) is an important cause of morbidity and mortality. It has a long asymptomatic phase, where routine blood tests cannot identify early functional losses, and therefore identifying common mechanisms across the many etiologies is an important goal.
OBJECTIVES
Our aim was to characterize serum, urine and tissue (kidney, lung, heart, spleen and liver) metabolomics changes in a rat model of CKD.
METHODS
A total of 17 male Wistar rats underwent 5/6 nephrectomy, whilst 13 rats underwent sham operation. Urine samples were collected weekly, for 6 weeks; blood was collected at weeks 0, 3 and 6; and tissue samples were collected at week 6. Samples were analyzed on a nuclear magnetic resonance spectroscopy platform with multivariate and univariate data analysis.
RESULTS
Changes in several metabolites were statistically significant. Allantoin was affected in all compartments. Renal asparagine, creatine, hippurate and trimethylamine were significantly different; in other tissues creatine, dimethylamine, dimethylglycine, trigonelline and trimethylamine were significant. Benzoate, citrate, dimethylglycine, fumarate, guanidinoacetate, malate, myo-inositol and oxoglutarate were altered in urine or serum.
CONCLUSION
Although the metabolic picture is complex, we suggest oxidative stress, the gut-kidney axis, acid-base balance, and energy metabolism as promising areas for future investigation.
简介
进行性慢性肾脏病（CKD）是发病率和死亡率的重要原因。它具有很长的无症状期，常规血液检查无法识别早期的功能丧失，因此确定多种病因的常见机制是一个重要目标。
目的
我们的目的是描述 CKD 大鼠模型中的血清、尿液和组织（肾脏、肺、心脏、脾脏和肝脏）代谢组学变化。
方法
总共 17 只雄性 Wistar 大鼠接受 5/6 肾切除术，而 13 只大鼠接受假手术。每周收集尿液样本，持续 6 周；在第 0、3 和 6 周收集血液；并在第 6 周收集组织样本。使用核磁共振波谱平台对样本进行分析，结合多变量和单变量数据分析。
结果
几种代谢物的变化具有统计学意义。所有的托因在所有隔室中都受到影响。肾脏天冬酰胺、肌酸、马尿酸和三甲胺差异显著；在其他组织中，肌酸、二甲胺、二甲基甘氨酸、瓜氨酸和三甲胺显著。苯甲酸盐、柠檬酸盐、二甲基甘氨酸、富马酸盐、胍基乙酸盐、苹果酸盐、肌醇和草酰乙酸盐在尿液或血清中发生改变。
结论
尽管代谢情况复杂，但我们认为氧化应激、肠道-肾脏轴、酸碱平衡和能量代谢是未来研究的有希望的领域。
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