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通过蛋白质组学研究评估血液透析膜材料的生物相容性

Biocompatibility assessment of haemodialysis membrane materials by proteomic investigations.

作者信息

Pieroni Luisa, Levi Mortera Stefano, Greco Viviana, Sirolli Vittorio, Ronci Maurizio, Felaco Paolo, Fucci Giorgio, De Fulviis Silvia, Massoud Renato, Condò Stefano, Capria Ambrogio, Di Daniele Nicola, Bernardini Sergio, Urbani Andrea, Bonomini Mario

机构信息

Department of Experimental Medicine and Surgery, University "Tor Vergata", Rome, Italy.

出版信息

Mol Biosyst. 2015 Jun;11(6):1633-43. doi: 10.1039/c5mb00058k.

Abstract

The exposure of blood to an artificial surface such as the haemodialysis membrane results in the nearly instantaneous deposition of a layer of plasma proteins. The composition of the protein layer profoundly influences all subsequent events, and to a large extent determines the biocompatibility of the biomaterial. In the present study, we examine the protein adsorption capacity and coagulation profiles of the polysulfone-based helixone material in comparison to cellulose triacetate. A differential profiling investigation using shotgun proteomics data-independent analysis was applied to eluates obtained with each membrane after a dialysis session, in order to assess the function of desorbed proteins. Functional classification and network analysis performed using bioinformatics tools shed light on the involvement of adsorbed proteins into important molecular processes, such as lipid transport and metabolism, cell growth differentiation and communication, and the coagulation cascade. The collected evidence was further validated by targeted mass spectrometry using selected reaction monitoring on proteotypic transitions of key protein effectors, confirming the different panels of adsorbed protein on each membrane. The coagulation profile during haemodialysis of patients under polysulfone-based helixone filter cartridges was also assessed showing a slightly higher platelet activation profile after the dialysis session. The overall collected evidence highlights a modulation of the coagulation biological pathway during haemodialysis, which is largely influenced by the biomaterial used.

摘要

血液暴露于诸如血液透析膜之类的人工表面会导致血浆蛋白层几乎立即沉积。蛋白质层的组成深刻影响所有后续事件,并在很大程度上决定了生物材料的生物相容性。在本研究中,我们将聚砜基螺旋材料与三醋酸纤维素进行比较,研究其蛋白质吸附能力和凝血情况。在透析过程后,对每种膜获得的洗脱液进行了使用鸟枪法蛋白质组学数据非依赖分析的差异分析研究,以评估解吸蛋白质的功能。使用生物信息学工具进行的功能分类和网络分析揭示了吸附蛋白质参与重要分子过程,如脂质转运和代谢、细胞生长分化和通讯以及凝血级联反应。通过对关键蛋白质效应物的蛋白型转变进行选择反应监测的靶向质谱进一步验证了收集到的证据,证实了每种膜上吸附蛋白质的不同组合。还评估了使用聚砜基螺旋滤筒的患者血液透析期间的凝血情况,结果显示透析后血小板活化情况略高。总体收集到的证据突出了血液透析期间凝血生物学途径的调节,这在很大程度上受所用生物材料的影响。

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