Schettler V, Wieland E, Methe H, Schuff-Werner P, Müller G A
Department of Nephrology and Rheumatology, Georg-August-University, Göttingen, FRG.
Nephrol Dial Transplant. 1998 Oct;13(10):2588-93. doi: 10.1093/ndt/13.10.2588.
Living cells are protected by free radical scavenging enzymes against oxygen radical-mediated damage. It has been suggested that granulocytes are activated on the surface of dialyser membranes, resulting in the generation of free radicals. We have recently reported a lack of plasma lipid peroxidation and unchanged glutathione peroxidase (GSH-Px) as well as glutathione reductase (GSSG-R) activities in red blood cells of haemodialysis patients. However, because mature red cells are free of DNA and RNA, free radical scavenging enzymes (FRSE) cannot be regulated on the gene level in response to an acute oxidative stress. In contrast to erythrocytes, granulocytes are nucleated cells and FRSE protein concentrations can therefore be modulated.
GSH-Px, GSSG-R, superoxide dismutase (SOD) activities and total glutathione (GSH) were determined spectrophotometrically using a Cobas Fara semi-automatic analyser in granulocytes of 31 healthy blood donors and in 28 patients with chronic renal failure (CRF) for more than 6 months before as well as immediately after a single dialysis treatment. Patients were treated either by haemodialysis (n = 17) using low-flux polysulphone membranes or by haemofiltration (n= 1l) usings high-flux polysulphone membranes.
Compared to healthy controls, SOD and GSSG-R activities were increased in granulocytes of HD and HF patients, GSH and GSH-Px were decreased before a single treatment. After dialysis SOD and GSH-PX activities were significantly induced by both HD and HF whereas GSSG-R activities and GSH were decreased.
These results show that the enzymatic defence against oxygen radicals can be induced in granulocytes of patients undergoing regular dialysis treatment, whereas the non-enzymatic defence is compromised as shown by decreased GSH concentrations, both suggesting increased oxidative stress.
活细胞受到自由基清除酶的保护，免受氧自由基介导的损伤。有人提出，粒细胞在透析膜表面被激活，从而导致自由基的产生。我们最近报告，血液透析患者的红细胞中缺乏血浆脂质过氧化，谷胱甘肽过氧化物酶（GSH-Px）以及谷胱甘肽还原酶（GSSG-R）活性未发生变化。然而，由于成熟红细胞不含DNA和RNA，自由基清除酶（FRSE）无法在基因水平上响应急性氧化应激进行调节。与红细胞不同，粒细胞是有核细胞，因此FRSE蛋白浓度可以被调节。
使用Cobas Fara半自动分析仪，通过分光光度法测定31名健康献血者以及28名慢性肾衰竭（CRF）患者超过6个月且在单次透析治疗前和治疗后立即采集的粒细胞中的GSH-Px、GSSG-R、超氧化物歧化酶（SOD）活性以及总谷胱甘肽（GSH）含量。患者分别接受使用低通量聚砜膜的血液透析（n = 17）或使用高通量聚砜膜的血液滤过（n = 11）治疗。
与健康对照组相比，血液透析和血液滤过患者的粒细胞中SOD和GSSG-R活性增加，单次治疗前GSH和GSH-Px降低。透析后，血液透析和血液滤过均显著诱导SOD和GSH-Px活性，而GSSG-R活性和GSH降低。
这些结果表明，接受定期透析治疗的患者的粒细胞中针对氧自由基的酶防御可以被诱导，而GSH浓度降低表明非酶防御受到损害，两者均提示氧化应激增加。
