尿毒症毒素和髓过氧化物酶在尿毒症状态中的各自作用。

Respective role of uraemic toxins and myeloperoxidase in the uraemic state.

作者信息

Capeillère-Blandin Chantal, Gausson Valérie, Nguyen Anh Thu, Descamps-Latscha Béatrice, Drüeke Tilman, Witko-Sarsat Véronique

机构信息

Université Paris 5, CNRS UMR 8601, 45 rue des Saints Pères, 75270 Paris Cedex 06, France.

出版信息

Nephrol Dial Transplant. 2006 Jun;21(6):1555-63. doi: 10.1093/ndt/gfl007. Epub 2006 Feb 13.

DOI:10.1093/ndt/gfl007

PMID:16476719

Abstract

BACKGROUND

In haemodialysis (HD) patients, advanced oxidation protein products (AOPP) were previously ascribed to oxidized plasma proteins, resulting mainly from increased myeloperoxidase (MPO) activity. The aim of the present study was to assess the mechanisms leading to the generation of AOPP during the course of chronic kidney disease including end-stage renal disease, with particular focus on AOPP and MPO characterization in the plasma at decreasing levels of kidney function.

METHODS

Phagocyte activation was evaluated by whole blood NADPH oxidase and MPO activities. In plasma, MPO protein concentration was quantified by ELISA and catalytic activity assayed by the spectrophotometric detection of phenol and 4-aminoantipyrine (AAP) co-oxidation in the presence of hydrogen peroxide (H(2)O(2)).

RESULTS

In HD patients, plasma AOPP concentration was linked to neutrophil oxidative activity. Such an association was not found in control subjects or predialysis patients, suggesting that in the latter, AOPP generation did not mainly result from MPO released by activated neutrophils. Similarly, plasma AOPP correlated with plasma MPO protein concentration in HD patients, but not in control subjects or predialysis patients, suggesting that in the latter AOPP did not predominantly result from MPO activity. This interpretation was supported by the observation of a greater degree of co-oxidation of phenol and AAP in the absence of H(2)O(2) in predialysis patients than in HD patients or control subjects. The contribution of MPO dramatically differed between predialysis and HD patients (2+/-5 vs 46+/-6%; P<0.001).

CONCLUSION

Our observations suggest that AOPP generation in predialysis patients mainly results from MPO-independent oxidation mechanisms.

摘要

背景

在血液透析（HD）患者中，晚期氧化蛋白产物（AOPP）以前被认为是氧化血浆蛋白，主要源于髓过氧化物酶（MPO）活性增加。本研究的目的是评估慢性肾脏病（包括终末期肾病）病程中导致AOPP生成的机制，特别关注肾功能下降时血浆中AOPP和MPO的特征。

方法

通过全血NADPH氧化酶和MPO活性评估吞噬细胞活化。在血浆中，通过ELISA定量MPO蛋白浓度，并通过在过氧化氢（H₂O₂）存在下分光光度法检测苯酚和4-氨基安替比林（AAP）的共氧化来测定催化活性。

结果

在HD患者中，血浆AOPP浓度与中性粒细胞氧化活性相关。在对照组或透析前患者中未发现这种关联，这表明在后者中，AOPP的生成并非主要源于活化中性粒细胞释放的MPO。同样，HD患者血浆AOPP与血浆MPO蛋白浓度相关，但对照组或透析前患者中不相关，这表明在后者中AOPP并非主要源于MPO活性。透析前患者在无H₂O₂时苯酚和AAP的共氧化程度高于HD患者或对照组，这一观察结果支持了上述解释。透析前患者和HD患者中MPO的贡献差异显著（2±5%对46±6%；P<0.001）。