| Endotoxin (lipopolysaccharide) is the major constituent of the outer membrane ofgram-negative bacteria, and lipid A is the toxic and active center. Medical researchindicates that manifestations such as systemic inflammatory response, syndromemultiple organ failure and other serious disease are attributed to lipopolysaccharidewhich is the primary cause of endotoxemia. Progress has made in the treatment ofendotoxemia, however, there has few effective and safe clinical solution. In recent years,there is a strong focus on adsorption therapy to removal endotoxin in blood purification.This thesis will explore the potential application value of the adsorbent for the treatmentof endotoxemia from the perspective of specific selection and biocompatibility.Objective: To prepare a new adsorbent with heparin space arm and polymyxinB(PMB) ligand, which can present high selectivity, high adsorption capacity and goodbiocompatibility, and to discuss its potential clinical application and significance forhemoperfusion to remove endotoxin.Methods: The carrier of chloromethyl polystyrene resin was activated byethanediamine and heparin space arm was grafted, then PMB ligand was immobilizedonto absorbent with glutaraldehyde; In vitro FITC-lipopolysaccharide（FITC-LPS）static adsorption was employed to characterize the adsorption properties on theabsorbent, and limulus amebocyte lysate was conducted to measure quantitively theadsorption capacity and rate, then the blood compatibility was evaluated.Results:(1)The immobilized quantity of heparin was about14μg/g with its initialconcentration of5mg/ml and reaction time more than24h.(2)The immobilized capacityof PMB ligand was17~18mg/g.(3) In vitro FITC-LPS static adsorption indicated theadsorption properties of the adsorbent with PMB ligand was superior to the other twowithout PMB ligand.(4) The adsorbent had the removal rate of endotoxin above70%with the adsorption equilibrium time about2hours.(5)Blood compatibility experimentshowed the absorbent had little negative effects on blood cells and plasma protein, theiradsorption rate were less than10%and20%.Conclusion: Heparin was contributed to improve the blood compatibility of theadsorbent, the PMB ligand exhibited the specific adsorption to LPS, and its removal rate of endotoxin could be above70%in a short time. The adsorbent presented a promisingclinical application in the treatment of endotoxemia. |
