Homolová Jordanka, Janovičová Ľubica, Konečná Barbora, Vlková Barbora, Celec Peter, Tóthová Ľubomíra, Bábíčková Janka
Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, 81108 Bratislava, Slovakia.
Institute of Pathophysiology, Faculty of Medicine, Comenius University, 81108 Bratislava, Slovakia.
Diagnostics (Basel). 2020 Mar 11;10(3):152. doi: 10.3390/diagnostics10030152.
Current diagnostic methods of acute kidney injury (AKI) have limited sensitivity and specificity. Tissue injury has been linked to an increase in the concentrations of extracellular DNA (ecDNA) in plasma. A rapid turnover of ecDNA in the circulation makes it a potential marker with high sensitivity. This study aimed to analyze the concentration of ecDNA in plasma in animal models of AKI. Three different fractions of ecDNA were measured-total ecDNA was assessed fluorometrically, while nuclear ecDNA (ncDNA) and mitochondrial DNA (mtDNA) were analyzed using quantitative real-time PCR. AKI was induced using four different murine models of AKI-bilateral ureteral obstruction (BUO), glycerol-induced AKI (GLY), ischemia-reperfusion injury (IRI) and bilateral nephrectomy (BNx). Total ecDNA was significantly higher in BUO ( < 0.05) and GLY ( < 0.05) compared to the respective control groups. ncDNA was significantly higher in BUO ( < 0.05) compared to SHAM. No significant differences in the concentrations of mtDNA were found between the groups. The plasma concentrations of different fractions of ecDNA are dependent on the mechanism of induction of AKI and warrant further investigation as potential surrogate markers of AKI.
急性肾损伤（AKI）的当前诊断方法敏感性和特异性有限。组织损伤与血浆中细胞外DNA（ecDNA）浓度升高有关。循环中ecDNA的快速周转使其成为具有高敏感性的潜在标志物。本研究旨在分析AKI动物模型中血浆ecDNA的浓度。测量了ecDNA的三个不同部分——总ecDNA通过荧光法评估，而核ecDNA（ncDNA）和线粒体DNA（mtDNA）则使用定量实时PCR进行分析。使用四种不同的AKI小鼠模型诱导AKI——双侧输尿管梗阻（BUO）、甘油诱导的AKI（GLY）、缺血再灌注损伤（IRI）和双侧肾切除术（BNx）。与各自的对照组相比，BUO组（<0.05）和GLY组（<0.05）的总ecDNA显著更高。与假手术组相比，BUO组的ncDNA显著更高（<0.05）。各组之间mtDNA浓度未发现显著差异。ecDNA不同部分的血浆浓度取决于AKI的诱导机制，作为AKI的潜在替代标志物值得进一步研究。
