Department of Pediatric Nephrology, Wrocław Medical University, M.Skłodowskiej-Curie 50/52, Wrocław, Poland.
Cell Stress Chaperones. 2011 Mar;16(2):163-71. doi: 10.1007/s12192-010-0228-4. Epub 2010 Sep 19.
Phenomena related to chronic kidney disease, such as atherosclerosis, aggravate with the introduction of dialysis. Matrix metalloproteinases (MMP) and factors modifying their activity, such as their tissue inhibitors (TIMP) or neutrophil gelatinase-associated lipocalin (NGAL), take part in the matrix turnover and the endothelial damage characteristic for atherogenesis. However, there are no data on the associations between these parameters and other known pro-atherogenic factors, or on the impact of various dialysis modalities on them. The aim of our study was to assess the serum concentrations of NGAL, MMP-7, MMP-9, and TIMP-1, as well as their correlations with human heat shock proteins (Hsp90α, anti-Hsp60), endothelial dysfunction (sE-selectin), and inflammation (hsCRP) in pediatric patients chronically dialyzed. Twenty-two children on automated peritoneal dialysis (APD), 17 patients on hemodialysis (HD) and 24 controls were examined. The serum concentrations of NGAL, MMP-7, MMP-9, TIMP-1, Hsp90α, anti-Hsp60, and sE-selectin were assessed by enzyme-linked immunosorbent assay (ELISA). The median values of NGAL, MMP-7, MMP-9, TIMP-1, and MMP-9/NGAL ratio were significantly elevated in all dialyzed children vs. controls and were higher in HD than in APD. The values of MMP-9/TIMP-1 and MMP-7/TIMP-1 ratios in the HD subjects were lower than those in the APD children. Hsp90α and anti-Hsp60 predicted the values of NGAL, MMPs, and TIMP-1. Additionally, sE-selectin was a predictor of NGAL levels, whereas NGAL predicted the MMP and TIMP-1 concentrations. The increased concentrations of examined parameters indicate the dysfunction of MMP/TIMP/NGAL system in the dialyzed children, more pronounced on hemodialysis. The discrepancies between dialysis modalities and correlations with heat shock proteins (HSPs) suggest that NGAL may be considered a novel stress protein, whereas MMP-7, MMP-9, and TIMP-1 may be regarded as indicators of stress response in the pediatric population on chronic dialysis.
与慢性肾脏病相关的现象，如动脉粥样硬化，随着透析的引入而恶化。基质金属蛋白酶（MMP）和调节其活性的因子，如组织抑制剂（TIMP）或中性粒细胞明胶酶相关脂质运载蛋白（NGAL），参与了基质转换和动脉粥样硬化特征性的内皮损伤。然而，目前还没有关于这些参数与其他已知的促动脉粥样硬化因子之间的关系，以及各种透析方式对它们的影响的数据。我们的研究目的是评估血清中 NGAL、MMP-7、MMP-9 和 TIMP-1 的浓度，以及它们与儿科慢性透析患者的人类热休克蛋白（Hsp90α、抗-Hsp60）、内皮功能障碍（sE-选择素）和炎症（hsCRP）之间的相关性。我们检查了 22 名接受自动腹膜透析（APD）的儿童、17 名接受血液透析（HD）的患者和 24 名对照组。通过酶联免疫吸附试验（ELISA）测定血清中 NGAL、MMP-7、MMP-9、TIMP-1、Hsp90α、抗-Hsp60 和 sE-选择素的浓度。与对照组相比，所有透析患儿的 NGAL、MMP-7、MMP-9、TIMP-1 和 MMP-9/NGAL 比值的中位数均显著升高，且 HD 患儿的水平高于 APD 患儿。HD 患者的 MMP-9/TIMP-1 和 MMP-7/TIMP-1 比值低于 APD 患儿。Hsp90α 和抗-Hsp60 预测了 NGAL、MMPs 和 TIMP-1 的值。此外，sE-选择素是 NGAL 水平的预测因子，而 NGAL 则预测了 MMP 和 TIMP-1 的浓度。检查参数的浓度升高表明，在透析儿童中 MMP/TIMP/NGAL 系统功能障碍，在血液透析中更为明显。透析方式的差异和与热休克蛋白（HSPs）的相关性表明，NGAL 可以被认为是一种新型应激蛋白，而 MMP-7、MMP-9 和 TIMP-1 可以被视为慢性透析儿科人群应激反应的指标。
Zotero 插件