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慢性血液透析中的氧化应激与贫血:生物活性膜的前景

Oxidative stress and anemia in chronic hemodialysis: the promise of bioreactive membranes.

作者信息

Cruz Dinna N, de Cal Massimo, Ronco Claudio

机构信息

Department of Nephrology, Ospedale San Bortolo and the International Renal Research Institute Vicenza (IRRIV), Vicenza, Italy.

出版信息

Contrib Nephrol. 2008;161:89-98. doi: 10.1159/000130413.

Abstract

Patients with advanced chronic kidney disease are characterized by an imbalance between pro- and antioxidant factors, and increased oxidative stress has been associated with complications of end-stage renal disease such as atherosclerosis, Beta2-microglobulin amyloidosis and anemia. Antioxidants such as vitamin E work by inhibiting LDL oxidation by oxidants and by limiting cellular response to oxidized LDL, and are potentially useful adjuncts to the usual medical therapy provided to such patients. In chronic hemodialysis (HD) patients, vitamin E therapy may be administered in the form of dietary supplementation, or as an integral part of the HD procedure in the form of bioreactive dialysis membranes, in which the blood surface has been modified with alpha-tocopherol. Since blood membrane interaction plays a key role in generating oxidative stress, direct free radical scavenging at the membrane site is a logical approach. Dialysis with vitamin E-coated membranes (VECM) is associated with an improvement in circulating biomarkers of lipid peroxidation. Other than antioxidant activity, the modified surface appears to render these dialyzers more biocompatible, in that cellulose-based membranes behave similar to synthetic dialyzers in terms of cytokine induction. In small studies in chromic HD patients, both dietary vitamin E supplementation as well as use of VECM have been associated with reduced RBC fragility, prolonged RBC lifespan, and improvements in hemoglobin and rHuEpo requirements. Newer VECM based on polysulfone bring us further down the road towards complete biocompatibility, and represent a promising therapy against oxidative stress in chronic HD patients.

摘要

晚期慢性肾病患者的特征是促氧化因子和抗氧化因子之间失衡,氧化应激增加与终末期肾病的并发症如动脉粥样硬化、β2微球蛋白淀粉样变和贫血有关。维生素E等抗氧化剂通过抑制氧化剂对低密度脂蛋白(LDL)的氧化以及限制细胞对氧化LDL的反应来发挥作用,并且可能是此类患者常规药物治疗的有用辅助手段。在慢性血液透析(HD)患者中,维生素E治疗可以通过饮食补充的形式进行,或者作为HD程序的一个组成部分,采用生物活性透析膜的形式,其中血液表面已用α-生育酚进行了修饰。由于血膜相互作用在产生氧化应激中起关键作用,在膜部位直接清除自由基是一种合理的方法。用维生素E包被的膜(VECM)进行透析与脂质过氧化循环生物标志物的改善有关。除了抗氧化活性外,修饰后的表面似乎使这些透析器具有更高的生物相容性,因为基于纤维素的膜在细胞因子诱导方面的表现与合成透析器相似。在针对慢性HD患者的小型研究中,饮食补充维生素E以及使用VECM都与降低红细胞脆性、延长红细胞寿命以及改善血红蛋白和重组人促红细胞生成素(rHuEpo)需求有关。基于聚砜的新型VECM使我们在实现完全生物相容性的道路上又迈进了一步,并且代表了一种针对慢性HD患者氧化应激的有前景的治疗方法。

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