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  本文選題：內(nèi)毒素　切入點：血液凈化　出處：《重慶大學》2012年碩士論文

【摘要】：細菌內(nèi)毒素是革蘭氏陰性菌外膜的脂多糖成分，類脂A是其活性中心。醫(yī)學研究表明血液中內(nèi)毒素水平與全身炎癥反應及多臟器衰竭等病癥有密切關系，是導致內(nèi)毒素血癥的主要原因。內(nèi)毒素血癥的治療已經(jīng)取得了一些進展，然而臨床治療上尚無安全有效的治療方法。目前通過血液凈化吸附療法去除內(nèi)毒素受到越來越多的關注，本論文則從吸附劑的特異選擇性和生物相容性的角度出發(fā)，探討所制備的血液凈化吸附劑在內(nèi)毒素血癥治療方面的潛在應用價值。 目的：設計出一種帶有肝素分子臂和多粘菌素B配基，用于清除內(nèi)毒素的高選擇性、高吸附量、良好血液相容性的血液凈化吸附劑，探討其在通過血液灌流方法治療內(nèi)毒素血癥方面的潛能和意義。 方法：采用氯甲基樹脂（氯球）為載體，經(jīng)乙二胺活化后引入肝素分子臂，，戊二醛將多粘菌素B配基固定于吸附劑；熒光標記內(nèi)毒素體外血漿靜態(tài)吸附實驗直接觀察材料的吸附性能，通過鱟試劑盒定量測定其體外吸附內(nèi)毒素的吸附量和吸附率；血液相容性實驗考察吸附前后對血細胞、血小板及血漿蛋白成分的影響。 結(jié)果：（1）肝素初始濃度為5mg/ml且反應時間不少于24h，在吸附劑的固定量能夠達到14μg/g左右。（2）PMB配基初始濃度為4mg/ml，反應時間不少于5h，吸附劑固定量能夠達到17~18mg/g。（3）體外FITC-LPS吸附實驗直接觀察到PMB吸附劑的吸附性能要優(yōu)于肝素化氯球和氯球。（4）吸附劑在2小時左右能夠達到吸附平衡，對血漿中內(nèi)毒素的去除率能夠達到70%以上。（5）對血細胞和血漿蛋白的吸附率分別小于10%和20%。 討論吸附劑引入肝素分子臂有助于改善其血液相容性，PMB配基對于內(nèi)毒素具有特異選擇性，并且能在較短時間對內(nèi)毒素的去除率達到70%以上，表明該吸附劑在內(nèi)毒素血癥治療方面具有一定的臨床應用前景。
[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.
【學位授予單位】：重慶大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R318.08

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本文編號：1688333