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贫血与慢性肾衰竭:谷胱甘肽氧化状态的潜在作用

Anemia and chronic renal failure: the possible role of the oxidative state of glutathione.

作者信息

Costagliola C, Romano L, Sorice P, Di Benedetto A

机构信息

Eye Clinic, 1st School of Medicine, University of Naples, Italy.

出版信息

Nephron. 1989;52(1):11-4. doi: 10.1159/000185575.

DOI:10.1159/000185575
PMID:2710264
Abstract

The authors have investigated the oxidative state of glutathione in red blood cells (RBC) and plasma from patients affected by chronic renal failure (CRF) and from age-matched healthy subjects. RBC-reduced glutathione (GSH) levels were significantly lower in CRF patients than in healthy subjects. Oxidized glutathione (GSSG) levels in plasma from CRF patients were higher than in plasma from controls. GSSG levels in RBC were similar in both groups. No differences were noted in GSH plasma levels between patients and controls. The GSSG/GSH ratios in RBC were similar in the two groups; on the contrary, the GSSG/GSH ratio in plasma was significantly higher in CRF patients. High levels of GSSG in plasma could exert two important effects on RBC: (1) inhibition of glucose-6-phosphate dehydrogenase activity, with a consequent alteration of the glutathione system; (2) GSSG easily reacts with hemoglobin to produce hemoglobin-glutathione mixed disulfides, with a consequent protein aggregation and precipitation. In vitro experiments have shown that RBC from CRF patients easily lyse when incubated with their same plasma, but not when incubated in saline buffer. Our results seem to demonstrate that plasma from CRF patients contains various oxidants which could affect the integrity of the glutathione system in RBC. This alteration could play a role in the pathogenesis of anemia in uremic patients.

摘要

作者研究了慢性肾衰竭(CRF)患者及年龄匹配的健康受试者红细胞(RBC)和血浆中谷胱甘肽的氧化状态。CRF患者红细胞中还原型谷胱甘肽(GSH)水平显著低于健康受试者。CRF患者血浆中氧化型谷胱甘肽(GSSG)水平高于对照组血浆。两组红细胞中的GSSG水平相似。患者与对照组血浆中GSH水平无差异。两组红细胞中的GSSG/GSH比值相似;相反,CRF患者血浆中的GSSG/GSH比值显著更高。血浆中高水平的GSSG可对红细胞产生两个重要影响:(1)抑制葡萄糖-6-磷酸脱氢酶活性,从而改变谷胱甘肽系统;(2)GSSG容易与血红蛋白反应生成血红蛋白-谷胱甘肽混合二硫化物,进而导致蛋白质聚集和沉淀。体外实验表明,CRF患者的红细胞与自身血浆孵育时容易裂解,但在生理盐水缓冲液中孵育时则不会。我们的结果似乎表明,CRF患者的血浆含有多种氧化剂,可能会影响红细胞中谷胱甘肽系统的完整性。这种改变可能在尿毒症患者贫血的发病机制中起作用。

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