Olszewska Maria
Z Katedry i Zakladu Biochemii i Chemii Pomorskicj Akademii Mcdyczncj w Szczecinic al. Powstańców Wlkp. 72, 70-111 Szczecin.
Ann Acad Med Stetin. 2004;50(1):41-52.
Direct contact of the blood with the dialysis membrane during hemodialysis elicits a series of changes in blood cells. White blood cell count and total lymphocyte number are reduced, neutrocytes are stimulated and degranulate, platelet adhesiveness is enhanced. Interactions of granulocytes with the dialysis membrane stimulate the production of ROS and activate aerobic reactions triggering oxidative stress. Red blood cells form the "first line of defense" during contact of the blood with the dialysis membrane. The effect of ROS on erythrocytes appears in the form of reduced osmotic resistance of their cellular membrane and susceptibility to disintegration which results in the release of small quantities of hemoglobin and significant reduction in the lifetime of these cells. Oxidative stress caused by contact of the blood with the dialysis membrane triggers defense mechanisms in the erythrocyte that protect against oxidative damage. Reports on the effects of hemodialysis on the antioxidant system of the blood in patients with chronic renal failure are conflicting and the present work was aimed at resolving some of the discord. The following questions were addressed: (1) Does hemodialysis affect the antioxidant system of the blood in patients with chronic renal failure? (2) Are there associations between parameters of hemodialysis and of the blood's antioxidant system? (3) Is supplementation with antioxidants needed in hemodialysed patients? The experiments were done at the Department of Biochemistry and Chemistry, Pomeranian Medical University. Plasma and erythrocytes were obtained from 42 patients aged 67.7 +/- 12.3 years, treated at the Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, due to chronic renal failure caused by chronic glomerulonephritis (n=16), pyelonephritis (n=12), diabetes (n=3), arterial hypertension (n=3) or other cause (gout, nephrolithiasis, n=8). The patients were assigned to two equal groups: 1--with end-stage renal failure on hemodialysis; 2--eated conservatively. Hemodialysis was done three times per week, 4 hours per session, using Fresenius dialysers with polysulfone membranes and bicarbonate buffer with glucose. The control group comprised 21 healthy volunteers. All groups were matched for age and gender. A 10 mL heparinized blood sample was collected twice from group 1 patients before and after dialysis directly from the dialysis catheter and once after an overnight fast from group 2 patients and controls. Glutathione concentration was determined in whole blood. Plasma was prepared by centrifugation and MDA, Se, Cu, Zn, and Fe levels were measured. SOD, GSH-Px, and CAT activities, MDA, Se, Cu, Zn, and Fe levels were determined in erythrocytes. Statistical methods were applied to determine significance of differences between groups and correlations between parameters studied.
(1) Hemodialysis leads to significant changes in the antioxidant system of the blood of patients with chronic renal failure. The effect is noticeable with antioxidant enzyme activities and concentrations of nonenzymatic components of the system. (2) The activity of erythrocyte GSH-Px decreases with time of dialysis potentiating the effects of oxidative stress. (3) Reduced erythrocyte levels of Se in dialysed patients correlate with lower GSH-Px activities. Selenium supplementation may be of benefit to the antioxidative defense mechanisms.
血液透析过程中血液与透析膜的直接接触会引发血细胞的一系列变化。白细胞计数和总淋巴细胞数量减少,中性粒细胞受到刺激并脱颗粒,血小板黏附性增强。粒细胞与透析膜的相互作用会刺激活性氧(ROS)的产生并激活有氧反应,引发氧化应激。红细胞在血液与透析膜接触过程中形成“第一道防线”。ROS对红细胞的影响表现为细胞膜渗透压抵抗力降低和易崩解,导致少量血红蛋白释放以及这些细胞寿命显著缩短。血液与透析膜接触引起的氧化应激会触发红细胞中的防御机制,以防止氧化损伤。关于血液透析对慢性肾衰竭患者血液抗氧化系统影响的报道相互矛盾,本研究旨在解决其中一些分歧。研究了以下问题:(1)血液透析是否会影响慢性肾衰竭患者的血液抗氧化系统?(2)血液透析参数与血液抗氧化系统参数之间是否存在关联?(3)血液透析患者是否需要补充抗氧化剂?实验在波美拉尼亚医科大学生物化学与化学系进行。从波美拉尼亚医科大学肾脏病、移植与内科治疗的42名年龄为67.7±12.3岁的患者中获取血浆和红细胞,这些患者因慢性肾小球肾炎(n = 16)、肾盂肾炎(n = 12)、糖尿病(n = 3)、动脉高血压(n = 3)或其他原因(痛风、肾结石,n = 8)导致慢性肾衰竭。患者被分为两个相等的组:1组——终末期肾衰竭接受血液透析;2组——保守治疗。每周进行三次血液透析,每次4小时,使用带有聚砜膜的费森尤斯透析器和含葡萄糖的碳酸氢盐缓冲液。对照组包括21名健康志愿者。所有组在年龄和性别上相匹配。从1组患者透析前和透析后直接从透析导管采集10 mL肝素化血样,从2组患者和对照组空腹过夜后采集一次血样。测定全血中的谷胱甘肽浓度。通过离心制备血浆,并测量丙二醛(MDA)、硒(Se)、铜(Cu)、锌(Zn)和铁(Fe)的水平。测定红细胞中的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH - Px)和过氧化氢酶(CAT)活性以及MDA、Se、Cu、Zn和Fe的水平。应用统计方法确定组间差异的显著性以及所研究参数之间的相关性。
(1)血液透析会导致慢性肾衰竭患者血液抗氧化系统发生显著变化。这种影响在抗氧化酶活性和系统非酶成分浓度方面很明显。(2)红细胞GSH - Px的活性随透析时间降低,增强了氧化应激的影响。(3)透析患者红细胞中Se水平降低与较低的GSH - Px活性相关。补充硒可能有益于抗氧化防御机制。