1H NMR-based metabolite profiling of plasma in a rat model of chronic kidney disease.
1H NMR-based metabolite profiling of plasma in a rat model of chronic kidney disease.
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DOI：
10.1371/journal.pone.0085445
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hwang GS
中科院分区：
文献类型：
--
作者：
Kim JA;Choi HJ;Kwon YK;Ryu DH;Kwon TH;Hwang GS
慢性肾脏病（CKD）的特征是肾功能逐渐丧失，从血液中排出废物和液体。利用基于1H NMR的代谢组学来研究通过手术减少肾质量诱导的患有CKD的大鼠中改变的代谢模式（即，5/6肾切除术（5/6 Nx）），特别是用于鉴定与早期CKD相关的特定代谢生物标志物。与假手术大鼠相比，在CKD大鼠（5/6 Nx后4周或8周）中进行血浆代谢物分析。主成分分析（PCA），偏最小二乘判别分析（PLS-DA）和正交偏最小二乘判别分析（OPLS-DA）评分图显示组间的显着分离。由此产生的代谢特征表明，CKD患者血浆中有机阴离子水平显著升高，包括柠檬酸盐、β-羟基丁酸盐、乳酸盐、乙酸盐、乙酰乙酸盐和甲酸盐。此外，丙氨酸、谷氨酰胺和谷氨酸的水平显著较高。这些变化可能与CKD中复杂的代谢性酸中毒有关，以抵消全身代谢性酸中毒或肌肉蛋白质代谢增加。与此相反，VLDL/LDL（CH 2）n和N-乙酰糖蛋白水平降低。总之，在CKD大鼠中观察到的血浆代谢产物谱的变化提供了对CKD早期代谢紊乱的见解，特别是对于酸碱和/或氨基酸的代谢改变。
Chronic kidney disease (CKD) is characterized by the gradual loss of the kidney function to excrete wastes and fluids from the blood. 1H NMR-based metabolomics was exploited to investigate the altered metabolic pattern in rats with CKD induced by surgical reduction of the renal mass (i.e., 5/6 nephrectomy (5/6 Nx)), particularly for identifying specific metabolic biomarkers associated with early of CKD. Plasma metabolite profiling was performed in CKD rats (at 4- or 8-weeks after 5/6 Nx) compared to sham-operated rats. Principle components analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) score plots showed a significant separation between the groups. The resulting metabolic profiles demonstrated significantly increased plasma levels of organic anions, including citrate, β-hydroxybutyrate, lactate, acetate, acetoacetate, and formate in CKD. Moreover, levels of alanine, glutamine, and glutamate were significantly higher. These changes were likely to be associated with complicated metabolic acidosis in CKD for counteracting systemic metabolic acidosis or increased protein catabolism from muscle. In contrast, levels of VLDL/LDL (CH2)n and N-acetylglycoproteins were decreased. Taken together, the observed changes of plasma metabolite profiles in CKD rats provide insights into the disturbed metabolism in early phase of CKD, in particular for the altered metabolism of acid-base and/or amino acids.
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