新型蛋白结合类毒素血液灌流吸附剂的制备及吸附性能

蛋白结合类毒素(PBUT)在尿毒症并发症的发生发展中起着重要作用, 现有血液净化模式对其清除效果较差, 开发用于高效清除尿毒症患者体内PBUT的血液灌流吸附材料已成为迫切的临床需求. 本文首先采用悬浮聚合法制备了咪唑基改性低交联聚苯乙烯微球P(St-DVB-VMZ); 然后通过小分子外交联剂的一步法傅克烷基化后交联反应, 制备出血液灌流用含咪唑基超高交联聚苯乙烯多孔树脂吸附剂HCP(St-DVB-VMZ). 利用傅里叶变换红外光谱(FTIR)、 X射线光电子能谱(XPS)、 扫描电子显微镜(SEM)及N₂吸附-脱附分析等表征了吸附树脂的化学结构和微观孔结构. 结果表明, HCP(St-DVB-VMZ)具有丰富的孔结构, 比表面积达到709 m²/g. 尿毒症毒素吸附实验结果表明, HCP(St-DVB-VMZ)对蛋白结合类毒素[对硫酸吲哚酚(IS)、 对甲酚硫酸盐(PCS)和吲哚乙酸(IAA)]和中大分子毒素[甲状旁腺激素(PTH)、 β₂-微球蛋白(β₂M)及白细胞介素6(IL-6)]均具有优异的吸附性能并展示出较好的血液相容性, 有望实现全血灌流临床应用.

Preparation and Property of A Novel Hemoperfusion Adsorbent For Protein-bound Uremic Toxins

Protein-bound uremic toxins（PBUTs）， as important risk factors for the progression of chronic kidney disease（CKD）， can’t be cleared efficiently by traditional hemodialysis method until now. Therefore， it still remains a challenge for developing hemoperfusion adsorbents with enhanced PBUTs removal efficiency. In this work， a facile， one-step method was developed for the synthesis of imidazole-based hypercrosslinked polystyrene porous adsorbent， HCP（St-DVB-VMZ）， using imidazole modified low crosslinked polystyrene microspheres， P（St-DVB-VMZ）， as precursor， followed by Friedel crafts alkylation reaction with small-molecule external cross-linking agent. The chemical structure and micro-pore structure of the adsorbent were characte-rized by Fourier transform infrared spectroscopy（FTIR）， X-ray photoelectron spectroscopy（XPS）， scanning electron microscopy（SEM） and N₂ adsorption-desorption analysis. The results demonstrated that HCP（St-DVB-VMZ） had abundant microporous structure， and the specific surface area was up to 709 m²/g. Adsorption experiments showed that the as-fabricated HCP（St-DVB-VMZ） exibited good removal capacity for both the PBUTs（IS， PCS and IAA） and the middle molecular toxins（PTH，β2M and IL-6）. The hemocompatibility assays indicated that the HCP（St-DVB-VMZ） possessed good in vitro hemocompatibility，making it suitable for contacting with blood as a hemoperfusion absorbent for clinical application.