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镰状细胞血管闭塞危象期间氧化应激的加剧与抗带3自身抗体率降低和红细胞衍生微粒水平升高相关:一项前瞻性研究。

Exacerbation of oxidative stress during sickle vaso-occlusive crisis is associated with decreased anti-band 3 autoantibodies rate and increased red blood cell-derived microparticle level: a prospective study.

作者信息

Hierso Régine, Lemonne Nathalie, Villaescusa Rinaldo, Lalanne-Mistrih Marie-Laure, Charlot Keyne, Etienne-Julan Maryse, Tressières Benoit, Lamarre Yann, Tarer Vanessa, Garnier Yohann, Hernandez Ada Arce, Ferracci Serge, Connes Philippe, Romana Marc, Hardy-Dessources Marie-Dominique

机构信息

Unité Biologie Intégrée du Globule Rouge, laboratoire d'Excellence GR-Ex, Université des Antilles, Inserm, U 1134, Pointe-à-Pitre, Guadeloupe.

CHU de Pointe-à-Pitre, Unité Transversale de la Drépanocytose, Pointe-à-Pitre, Guadeloupe.

出版信息

Br J Haematol. 2017 Mar;176(5):805-813. doi: 10.1111/bjh.14476. Epub 2016 Dec 16.

Abstract

Painful vaso-occlusive crisis, a hallmark of sickle cell anaemia, results from complex, incompletely understood mechanisms. Red blood cell (RBC) damage caused by continuous endogenous and exogenous oxidative stress may precipitate the occurrence of vaso-occlusive crises. In order to gain insight into the relevance of oxidative stress in vaso-occlusive crisis occurrence, we prospectively compared the expression levels of various oxidative markers in 32 adults with sickle cell anaemia during vaso-occlusive crisis and steady-state conditions. Compared to steady-state condition, plasma levels of free haem, advanced oxidation protein products and myeloperoxidase, RBC caspase-3 activity, as well as the concentrations of total, neutrophil- and RBC-derived microparticles were increased during vaso-occlusive crises, whereas the reduced glutathione content was decreased in RBCs. In addition, natural anti-band 3 autoantibodies levels decreased during crisis and were negatively correlated with the rise in plasma advanced oxidation protein products and RBC caspase-3 activity. These data showed an exacerbation of the oxidative stress during vaso-occlusive crises in sickle cell anaemia patients and strongly suggest that the higher concentration of harmful circulating RBC-derived microparticles and the reduced anti-band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates.

摘要

疼痛性血管闭塞危象是镰状细胞贫血的一个标志,其由复杂且尚未完全理解的机制导致。持续的内源性和外源性氧化应激引起的红细胞(RBC)损伤可能促使血管闭塞危象的发生。为了深入了解氧化应激在血管闭塞危象发生中的相关性,我们前瞻性地比较了32例成年镰状细胞贫血患者在血管闭塞危象期间和稳定状态下各种氧化标志物的表达水平。与稳定状态相比,血管闭塞危象期间游离血红素、晚期氧化蛋白产物和髓过氧化物酶的血浆水平、红细胞半胱天冬酶 - 3活性以及总微粒、中性粒细胞衍生微粒和红细胞衍生微粒的浓度均升高,而红细胞中还原型谷胱甘肽含量降低。此外,天然抗带3自身抗体水平在危象期间下降,且与血浆晚期氧化蛋白产物升高和红细胞半胱天冬酶 - 3活性呈负相关。这些数据表明镰状细胞贫血患者在血管闭塞危象期间氧化应激加剧,强烈提示有害的循环红细胞衍生微粒浓度升高和抗带3自身抗体水平降低可能都与氧化型带3募集到膜聚集体有关。

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