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原发性醛固酮增多症患者的红细胞改变。

Human red blood cells alterations in primary aldosteronism.

机构信息

Department of Molecular Medicine-Biological Chemistry, University of Padua, Viale G. Colombo 3, 35131 Padua, Italy.

出版信息

J Clin Endocrinol Metab. 2013 Jun;98(6):2494-501. doi: 10.1210/jc.2012-3571. Epub 2013 Mar 28.

Abstract

CONTEXT

Aldosterone (Aldo) effects include NADPH oxidase activation involved in Aldo-related oxidative stress. Red blood cells (RBCs) are particularly sensitive to oxidative assault, and both the formation of high molecular weight aggregates (HMWAs) and the diamide-induced Tyr phosphorylation (Tyr-P) level of membrane band 3 can be used to monitor their redox status.

OBJECTIVE

The Aldo-related alterations in erythrocytes were evaluated by comparing in vitro evidence.

DESIGN

This was a multicenter comparative study.

STUDY PARTICIPANTS

The study included 12 patients affected by primary aldosteronism (PA) and 6 healthy control subjects (HCs), whose RBCs were compared with those of patients with PA. For in vitro experiments, RBCs from HCs were incubated with increasing Aldo concentrations.

MAIN OUTCOME MEASURES

The Tyr-P level, band 3 HMWA formation, and autologous IgG binding were evaluated.

RESULTS

In patients with PA, both Tyr-P levels and band 3 HMWAs were higher than those in HCs. RBCs from HCs were treated with increasing Aldo concentrations in both platelet-poor plasma (PPP) and charcoal-stripped (CS)-PPP. Results showed that Aldo had dose- and time-dependent effects on band 3 Tyr-P and HMWA formation in CS-PPP more than in PPP. These effects were almost completely prevented by canrenone or cortisol. Aldo-related membrane alterations led to increased autologous IgG binding.

CONCLUSIONS

Erythrocytes from patients with PA show oxidative-like stress evidenced by increased HMWA content and diamide-induced band 3 Tyr-P level. Aldo effects are mediated by the mineralocorticoid receptor, as suggested by the inhibitory effects of canrenone, an antagonist of Aldo. In CS-PPP, in which Aldo induces remarkable membrane alterations leading to IgG binding, Aldo may be responsible for premature RBC removal from circulation.

摘要

背景

醛固酮(Aldo)的作用包括参与醛固酮相关氧化应激的 NADPH 氧化酶激活。红细胞(RBC)对氧化攻击特别敏感,高分子量聚集物(HMWAs)的形成和膜带 3 的二酰胺诱导的酪氨酸磷酸化(Tyr-P)水平均可用于监测其氧化还原状态。

目的

通过比较体外证据评估红细胞中的 Aldo 相关变化。

设计

这是一项多中心比较研究。

研究参与者

该研究包括 12 例原发性醛固酮增多症(PA)患者和 6 例健康对照者(HCs),比较了他们的 RBC。对于体外实验,将 HCs 的 RBC 与 PA 患者的 RBC 一起孵育,用递增浓度的 Aldo 处理。

主要观察指标

评估 Tyr-P 水平、带 3 HMWAs 形成和自身 IgG 结合。

结果

PA 患者的 Tyr-P 水平和带 3 HMWAs 均高于 HCs。在血小板贫乏血浆(PPP)和活性炭处理的(CS)-PPP 中,用递增浓度的 Aldo 处理来自 HCs 的 RBC。结果表明,Aldo 在 CS-PPP 中对带 3 Tyr-P 和 HMWAs 形成具有剂量和时间依赖性的影响,而在 PPP 中则不然。这些作用几乎完全被坎利酮或皮质醇所预防。Aldo 相关的膜改变导致自身 IgG 结合增加。

结论

PA 患者的 RBC 显示出氧化样应激,表现为 HMWAs 含量增加和二酰胺诱导的带 3 Tyr-P 水平升高。Aldo 作用是通过盐皮质激素受体介导的,如 Aldo 拮抗剂坎利酮的抑制作用所表明的那样。在 CS-PPP 中,Aldo 可诱导显著的膜改变导致 IgG 结合,Aldo 可能导致 RBC 从循环中过早清除。

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