Abstract: High concentration of bilirubin may cause neurotoxicity, permanent brain damage, and even death in severe cases.It is difficult to remove bilirubin from serum by circulated adsorption, because bilirubin can be tightly bound with albumin as a complex in human serum.The albumin in the complex has a larger volume than that of bilirubin, which results in high steric hindrance of adsorption or displacement of bilirubin.In order to enhance serum bilirubin adsorption capacity, five kinds of amines and eight kinds of amino acids as specific ligands were immobilized on cellulose acetate (CA)/polyethyleneimine (PEI) membrane via the glutaraldehyde modification method.Experimental results indicated that although the primary amine contents of modified membranes were only one third of CA/PEI membrane, bilirubin adsorption capacities of four kinds of modified membranes increased by more than 100%. Moreover,the adsorption selectivity of the four modified membranes for bilirubin/human albumin pair was greater than that of CA/PEI membrane. Prolongation of the spacer and immobilization of specific ligand could be the cause of such results.Ligand composition had a significant influence on bilirubin adsorption capacity.The ligands containing hydrophobic and primary amino groups could enhance bilirubin adsorption capacity, and the ligands with carboxyl radicals could decrease bilirubin adsorption capacity of the modified membrane.Moreover, ligand density, ligand steric hindrance, and other factors could also influence bilirubin adsorption capacity.In the experiments, the ligands containing high steric hindrance groups, such as phenyl groups had a negative effect on bilirubin adsorption capacity of the modified membrane, and its bilirubin adsorption capacity could not be enhanced via increasing ligand density.However, bilirubin adsorption capacity of the membrane modified with low steric hindrance ligand, for example hexamethylene-diamine (3-HMD)-modified membrane, increased with increasing ligand density.

Key words: bilirubin, amine acids, ligand density, steric hindrance, affinity membrane

摘要： 体内存在过量的胆红素会引起神经系统疾病,严重时危及生命,常用循环吸附法去除,但是多数胆红素与白蛋白形成复合物,难于拆分,导致血清胆红素的吸附去除率降低。以醋酸纤维素/聚乙烯基亚胺共混亲和膜(CA/PEI膜)为基质,通过戊二醛活化,引入间隔臂,固载具有一定特异性吸附的5种有机胺和8种氨基酸配基,强化血清胆红素的去除效果。研究结果表明,虽然改性膜的伯胺基含量仅为CA/PEI膜的1/3,但是因间隔臂的引入和配基特异性的增强,4种改性膜的胆红素吸附量提高了100%以上,并且提高了胆红素相对于蛋白的吸附选择性。增加胺基和疏水结构有利于胆红素的吸附;羧基不利于胆红素吸附;胆红素吸附还受到配基密度和空间位阻等诸多因素的影响。苯环等空间位阻较大的配基,不利于实际胆红素的吸附,且无法通过提高配基密度而提高其改性膜的胆红素吸附量,而含直链胺配基的己二胺(3-HMD)改性膜的胆红素吸附量随配基密度的提高而提高。

关键词: 胆红素, 氨基酸, 配基密度, 空间位阻, 亲和膜