一种新型内毒素特异吸附的血液净化材料的制备与性能研究

发布时间：2018-03-31 00:24

本文选题：内毒素　切入点：血液净化　出处：《重庆大学》2012年硕士论文

【摘要】：细菌内毒素是革兰氏阴性菌外膜的脂多糖成分，类脂A是其活性中心。医学研究表明血液中内毒素水平与全身炎症反应及多脏器衰竭等病症有密切关系，是导致内毒素血症的主要原因。内毒素血症的治疗已经取得了一些进展，然而临床治疗上尚无安全有效的治疗方法。目前通过血液净化吸附疗法去除内毒素受到越来越多的关注，本论文则从吸附剂的特异选择性和生物相容性的角度出发，探讨所制备的血液净化吸附剂在内毒素血症治疗方面的潜在应用价值。目的：设计出一种带有肝素分子臂和多粘菌素B配基，用于清除内毒素的高选择性、高吸附量、良好血液相容性的血液净化吸附剂，探讨其在通过血液灌流方法治疗内毒素血症方面的潜能和意义。方法：采用氯甲基树脂（氯球）为载体，经乙二胺活化后引入肝素分子臂，，戊二醛将多粘菌素B配基固定于吸附剂；荧光标记内毒素体外血浆静态吸附实验直接观察材料的吸附性能，通过鲎试剂盒定量测定其体外吸附内毒素的吸附量和吸附率；血液相容性实验考察吸附前后对血细胞、血小板及血浆蛋白成分的影响。结果：（1）肝素初始浓度为5mg/ml且反应时间不少于24h，在吸附剂的固定量能够达到14μg/g左右。（2）PMB配基初始浓度为4mg/ml，反应时间不少于5h，吸附剂固定量能够达到17~18mg/g。（3）体外FITC-LPS吸附实验直接观察到PMB吸附剂的吸附性能要优于肝素化氯球和氯球。（4）吸附剂在2小时左右能够达到吸附平衡，对血浆中内毒素的去除率能够达到70%以上。（5）对血细胞和血浆蛋白的吸附率分别小于10%和20%。讨论吸附剂引入肝素分子臂有助于改善其血液相容性，PMB配基对于内毒素具有特异选择性，并且能在较短时间对内毒素的去除率达到70%以上，表明该吸附剂在内毒素血症治疗方面具有一定的临床应用前景。
[Abstract]:Bacterial endotoxin is the lipopolysaccharide component of the outer membrane of Gram-negative bacteria and lipopolysaccharide A is its active center.Medical studies show that the level of endotoxin in blood is closely related to systemic inflammation and multiple organ failure, which is the main cause of endotoxemia.Some progress has been made in the treatment of endotoxemia. However, there is no safe and effective treatment for endotoxemia.At present, more and more attention has been paid to endotoxin removal by blood purification and adsorption therapy. In this paper, the specific selectivity and biocompatibility of adsorbents are considered.To explore the potential application value of blood purification adsorbent in endotoxemia treatment.Objective: to design a blood purification adsorbent with heparin molecular arm and polymyxin B ligand for removing endotoxin with high selectivity, high adsorption and good blood compatibility.To explore its potential and significance in the treatment of endotoxemia through hemoperfusion.Methods: chloromethyl resin (chloromethyl) was used as carrier and heparin molecular arm was introduced after activation by ethylenediamine. Glutaraldehyde ligand group of polymyxin B was immobilized on the adsorbent.The static adsorption of endotoxin in plasma was observed directly by fluorescence labeled endotoxin in vitro. The adsorption capacity and adsorption rate of endotoxin in vitro were measured quantitatively by Limulus lysate kit, and the blood cells before and after adsorption were investigated by blood compatibility test.Effects of platelet and plasma protein components.Results the initial concentration of heparin was 5mg/ml and the reaction time was not less than 24 h. When the immobilization amount of adsorbent was about 14 渭 g / g, the initial concentration of PMB ligand was 4 mg / ml, the reaction time was not less than 5 h, the amount of adsorbent fixation could reach 17 ~ 18 mg / g 路g ~ (-3)).It was observed directly that the adsorption performance of PMB adsorbent was better than that of heparin chloride ball and chlorine sphere. 4) the adsorption equilibrium of the adsorbent was achieved in about 2 hours.The removal rate of endotoxin in plasma was more than 70%. The adsorption rates of blood cells and plasma proteins were less than 10% and 20%, respectively.It is discussed that the introduction of heparin molecule arm can improve the blood compatibility of heparin molecule arm and the PMB ligand has specific selectivity for endotoxin, and the removal rate of endotoxin can reach more than 70% in a short time.It shows that the adsorbent has a certain clinical application prospect in the treatment of endotoxemia.
【学位授予单位】：重庆大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R318.08

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