关键词: 胆红素, 氨基酸, 配基密度, 空间位阻, 亲和膜

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