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2 型糖尿病患者肾脏改变的早期尿液生物标志物的蛋白质组学分析。

Proteomic analysis of early urinary biomarkers of renal changes in type 2 diabetic patients.

机构信息

Department of Biomedical Science, University of Modena and Reggio Emilia Modena, Italy; Diagnostic and Laboratory Services, University of Modena and Reggio Emilia Modena, Italy.

出版信息

Proteomics Clin Appl. 2008 Apr;2(4):478-91. doi: 10.1002/prca.200780109. Epub 2008 Mar 7.

Abstract

Diabetic nephropathy (DN) is a complication associated with diabetes, leading to end-stage renal disease (ESRD). Despite significant progress in understanding DN, the cellular mechanisms leading to the renal damage are incompletely defined. In this study, with the aim to identify urine biomarkers for the early renal alterations in type 2 diabetes mellitus (T2D), we performed urinary proteomic analysis of 10 normoalbuminuric patients with T2D, 12 patients with type 2 DN (T2DN), and 12 healthy subjects. Proteins were separated by 2-DE and identified with ESI-Q-TOF MS/MS. Comparing the patients proteomic profiles with those of normal subjects, we identified 11 gradually differently changed proteins. The decreased proteins were the prostatic acid phosphatase precursor, the ribonuclease and the kallikrein-3. Eight proteins were progressively increased in both patients groups: transthyretin precursor, Ig κ chain C region, Ig κ chain V-II region Cum, Ig κ-chain V-III region SIE, carbonic anhydrase 1, plasma retinol-binding protein, β-2-microglobulin precursor, β-2-glycoprotein 1. The proteomic analysis allowed us to identify several increased urinary proteins, not only in T2DN but also in T2D patients in which the microalbuminuria was in the normal range. These patterns of urinary proteins might represent a potential tool for a better understanding of diabetic renal damage.

摘要

糖尿病肾病(DN)是一种与糖尿病相关的并发症,可导致终末期肾病(ESRD)。尽管对 DN 的发病机制有了深入的了解,但导致肾脏损伤的细胞机制仍不完全明确。在这项研究中,我们旨在寻找 2 型糖尿病(T2D)早期肾脏改变的尿液生物标志物,对 10 名正常白蛋白尿的 T2D 患者、12 名 2 型糖尿病肾病(T2DN)患者和 12 名健康对照者进行了尿液蛋白质组学分析。通过 2-DE 分离蛋白质,并采用 ESI-Q-TOF MS/MS 进行鉴定。将患者的蛋白质组图谱与正常对照者进行比较,我们鉴定出 11 个逐渐改变的蛋白质。下降的蛋白质包括前列腺酸性磷酸酶前体、核糖核酸酶和激肽释放酶 3。两个患者组均逐渐增加了 8 种蛋白质:转甲状腺素蛋白前体、免疫球蛋白κ轻链 C 区、免疫球蛋白κ轻链 V-II 区 Cum、免疫球蛋白κ轻链 V-III 区 SIE、碳酸酐酶 1、血浆视黄醇结合蛋白、β-2-微球蛋白前体和β-2-糖蛋白 1。蛋白质组学分析使我们能够鉴定出几种尿液中增加的蛋白质,不仅在 T2DN 患者中,而且在微量白蛋白尿正常的 T2D 患者中也有增加。这些尿液蛋白质的模式可能代表了更好地了解糖尿病肾脏损伤的潜在工具。

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