新型蛋白结合类毒素血液灌流吸附剂的制备及吸附性能

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

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 m^(2)/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.

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 characterized 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-DVBVMZ)had abundant microporous structure,and the specific surface area was up to 709 m^(2)/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.