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通过用聚多巴胺涂层固定 FXa 抑制剂来制备一种抗凝血聚醚砜膜。

Preparation of an anticoagulant polyethersulfone membrane by immobilizing FXa inhibitors with a polydopamine coating.

机构信息

Department of Nephrology, Xiangya Hospital of Central South University, Changsha, Hunan, China.

Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, Hunan, China.

出版信息

J Biomater Sci Polym Ed. 2024 Nov;35(16):2469-2483. doi: 10.1080/09205063.2024.2384275. Epub 2024 Jul 31.

DOI:10.1080/09205063.2024.2384275
PMID:39082937
Abstract

Anticoagulation treatment for patients with high bleeding risk during hemodialysis is challenging. Contact between the dialysis membrane and the blood leads to protein adsorption and activation of the coagulation cascade reaction. Activated coagulation Factor X (FXa) plays a central role in thrombogenesis, but anticoagulant modification of the dialysis membrane is rarely targeted at FXa. In this study, we constructed an anticoagulant membrane using the polydopamine coating method to graft FXa inhibitors (apixaban and rivaroxaban) on the membrane surface. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) were used to characterize the membranes. The apixaban- and rivaroxabanmodified membranes showed lower water contact angles, decreased albumin protein adsorption, and suppressed platelet adhesion and activation compared to the unmodified PES membranes. Moreover, the modified membranes prolonged the blood clotting times in both the intrinsic and extrinsic coagulation pathways and inhibited FXa generation and complement activation, which suggested that the modified membrane enhanced biocompatibility and antithrombotic properties through the inhibition of FXa. Targeting FXa to design antithrombotic HD membranes or other blood contact materials might have great application potential.

摘要

在血液透析过程中,高出血风险患者的抗凝治疗颇具挑战性。透析膜与血液接触会导致蛋白质吸附和凝血级联反应的激活。活化的凝血因子 X (FXa) 在血栓形成中起着核心作用,但抗凝修饰透析膜很少针对 FXa。在这项研究中,我们使用聚多巴胺涂层法构建了一种抗凝膜,在膜表面接枝 FXa 抑制剂(阿哌沙班和利伐沙班)。衰减全反射-傅里叶变换红外光谱 (ATR-FTIR)、X 射线光电子能谱 (XPS)、扫描电子显微镜 (SEM) 和原子力显微镜 (AFM) 用于对膜进行表征。与未修饰的 PES 膜相比,阿哌沙班和利伐沙班修饰的膜具有较低的水接触角、减少的白蛋白蛋白吸附以及抑制血小板黏附和激活的作用。此外,修饰的膜延长了内源性和外源性凝血途径中的血液凝固时间,并抑制了 FXa 的产生和补体的激活,这表明修饰的膜通过抑制 FXa 增强了生物相容性和抗血栓形成特性。针对 FXa 设计抗血栓形成的 HD 膜或其他血液接触材料可能具有巨大的应用潜力。

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