The effect of electronegativity and angiotensin-converting enzyme inhibition on the kinin-forming capacity of polyacrylonitrile dialysis membranes
The effect of electronegativity and angiotensin-converting enzyme inhibition on the kinin-forming capacity of polyacrylonitrile dialysis membranes
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DOI：
10.1016/j.biomaterials.2007.11.019
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发表时间：
2008-03-01
期刊：
影响因子：
14
通讯作者：
Adam, Albert
中科院分区：
文献类型：
--
作者：
Desormeaux, Anik;Moreau, Marie Eve;Adam, Albert
带负电的膜和血管紧张素 I 转换酶抑制剂 (ACEi) 的组合会在血液透析过程中引起超敏反应 (HSR)，并且推测缓激肽 (BK) 相关肽是造成这些并发症的原因。在这项研究中，我们测试了通过涂覆聚乙烯亚胺层（AN69-ST 膜）来中和聚丙烯腈 AN69 膜的膜电负性（zeta 电位）对血液与合成膜接触诱导的激肽生成的影响。我们在离体血浆模型中使用带有 AN69 或 AN69-ST 膜的微型透析器，结果表明，用 AN69 膜进行血浆透析会导致显着的 BK 和 des-Arg(9)-BK 释放，而 ACEi 会增强这种释放。即使存在 ACEi，AN69-ST 膜也会显着减少这种激肽的形成，并且这些膜在透析液中的激肽回收率也显着降低。通过对覆盖两膜的蛋白质层进行免疫印迹检测的高分子量激肽原和因子 XII 证实了结果：这些蛋白质的结合和 AN69-ST 膜上的接触系统激活减少。这种应用于血浆、透析液和透析膜的离体实验模型可用于表征任何可能在体内与调节激肽药理活性的药物组合使用的生物材料的激肽形成能力。 (C) 2007 Elsevier Ltd. 保留所有权利。
The combination of negatively-charged membranes and angiotensin I-converting enzyme inhibitors (ACEi) evokes hypersensitivity reactions (HSR) during hemodialysis and bradykinin (BK)-related peptides have been hypothesized as being responsible for these complications. In this study, we tested the effects of neutralizing the membrane electronegativity (zeta potential) of polyacrylonitrile AN69 membranes by coating a polyethyleneimine layer (AN69-ST membranes) over the generation of kinins induced by blood contact with synthetic membranes. We used minidialyzers with AN69 or AN69-ST membranes in an ex vivo model of plasma and we showed that plasma dialysis with AN69 membranes led to significant BK and des-Arg(9)-BK release, which was potentiated by ACEi. This kinin formation was dramatically decreased by AN69-ST membranes, even in the presence of an ACEi, and kinin recovery in the dialysates was also significantly lower with these membranes. High molecular weight kininogen and factor XII detection by immunoblotting of the protein layer coating both membranes corroborated the results: binding of these proteins and contact system activation on AN69-ST membranes were reduced. This ex vivo experimental model applied to the plasma, dialysate and dialysis membrane could be used for the characterization of the kinin-forming capacity of any biomaterial potentially used in vivo in combination with drugs which modulate the pharmacological activity of kinins. (C) 2007 Elsevier Ltd. All rights reserved.