Du Ying Jun, Brash John L, McClung Glen, Berry Leslie R, Klement Petr, Chan Anthony K C
The Henderson Research Centre, McMaster University, 711 Concession Street, Ontario, Canada.
J Biomed Mater Res A. 2007 Jan;80(1):216-25. doi: 10.1002/jbm.a.30977.
Highly anticoagulant covalent antithrombin-heparin complex (ATH) was covalently grafted onto polyurethane catheters to suppress adsorption/activation of procoagulant proteins and enhance adsorption/activation of anticoagulant proteins for blood compatibility. Consistency of catheter coating was demonstrated using immunohistochemical visualization of ATH. The ability of the resulting immobilized ATH heparin chains to bind antithrombin (AT) from plasma, as measured by binding of (125)I-radiolabeled AT, was greater than that for commercially-available heparin-coated catheters, and much greater than for uncoated catheters. Complementary measurements of antifactor Xa (FXa) activity and plasma protein binding were also performed. Both ATH-coated and heparin-coated catheters demonstrated functional binding of exogenous AT. However, the ATH-coated catheters gave a trend towards elevated anti- FXa activities/AT binding ratios, consistent with the higher active pentasaccharide content in starting ATH. Western blot analysis of proteins adsorbed to catheters after incubation with rabbit plasma established protein binding profiles that showed AT and albumin as major plasma proteins adsorbed to ATH-coated catheters, while AT and altered forms of fibrinogen were major plasma protein species adsorbed to heparinized catheters.
将高抗凝性共价抗凝血酶 - 肝素复合物（ATH）共价接枝到聚氨酯导管上，以抑制促凝血蛋白的吸附/活化，并增强抗凝血蛋白的吸附/活化，从而提高血液相容性。通过ATH的免疫组织化学可视化证明了导管涂层的一致性。用（125）I放射性标记的抗凝血酶（AT）的结合来测量，所得固定化ATH肝素链与血浆中抗凝血酶（AT）结合的能力大于市售肝素涂层导管，远大于未涂层导管。还进行了抗Xa因子（FXa）活性和血浆蛋白结合的补充测量。ATH涂层导管和肝素涂层导管均显示出对外源性AT的功能性结合。然而，ATH涂层导管的抗FXa活性/AT结合比有升高趋势，这与起始ATH中较高的活性五糖含量一致。用兔血浆孵育后，对吸附在导管上的蛋白质进行蛋白质印迹分析，确定了蛋白质结合谱，显示AT和白蛋白是吸附在ATH涂层导管上的主要血浆蛋白，而AT和纤维蛋白原的改变形式是吸附在肝素化导管上的主要血浆蛋白种类。
