Vorapaxar-Modified Polysulfone Membrane with High Hemocompatibility Inhibits Thrombosis
Vorapaxar-Modified Polysulfone Membrane with High Hemocompatibility Inhibits Thrombosis
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Vorapaxar 修饰的高血液相容性聚砜膜可抑制血栓形成
DOI：
10.1016/j.msec.2020.111508
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
彭捷
中科院分区：
文献类型：
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作者：
刘薇;府晓;刘雁峰;苏涛;彭捷
血液透析治疗适用于患有肾功能不全、胰腺炎和其他严重疾病的患者。血小板是血液透析膜引起血栓形成的重要活性成分。到目前为止，很少有关于血液透析膜的研究关注蛋白酶激活受体1（PAR 1）活化对血小板膜的影响。在众多的抗血栓药物中，伏拉帕沙是一种新型的高效PAR 1抑制剂。在这项研究中，我们构建了一个vorapaxar改性聚砜（VMPSf）膜，采用浸渍-沉淀相转化方法，其特征在于在亲水性和机械性能方面的微观结构。VMPSf膜的水接触角比PSf膜的水接触角小22.45%。使用扫描电子显微镜获得血小板形态的集中测定。同时，我们评估了VMPSf膜对血小板粘附的影响。我们观察到，VMPSf膜可以减少粘附的血小板的数量，而不改变它们的球形或椭圆形。在VMPSf膜中的PAR 1水平比PSf膜中的PAR 1水平低7.4MFI，表明这种改性膜可以有效地抑制血小板活化。活化部分凝血活酶时间（APTT，延长5.3 s）和凝血酶时间（TT，延长2.1 s）反映了良好的抗凝特性。再钙化时间（延长80.6 s）和纤维蛋白原吸附（减少9.9 μg/cm 2）与抗血栓性质相关。为了确定VMPSf膜的生物安全性，我们研究了体外抗过敏和抗炎特性以及体内急性毒性，显然C3 a和C5 a分别降低至9.6和0.8 ng/mL。实验结果表明，VMPSf膜具有良好的临床应用前景。
Hemodialysis therapy is intended for patients suffering from renal insufficiency, pancreatitis, and other serious diseases. Platelets are an important active ingredient in the thrombosis induced by hemodialysis membranes. So far, there are few studies of hemodialysis membranes focusing on the effects of protease-activated receptor 1 (PAR1) activation on the platelet membrane. Among various antithrombotic agents, vorapaxar is a novel PAR1 inhibitor with high efficacy. In this study, we constructed a vorapaxar-modified polysulfone (VMPSf) membrane using immersion-precipitation phase transformation methods and characterized the microstructure in terms of hydrophilicity and mechanical properties. The water contact angle of the VMPSf membrane was 22.45% lower than that of the PSf membrane. A focused determination of platelet morphology was obtained using scanning electron microscopy. Meanwhile, we evaluated the effects of a VMPSf membrane on platelet adhesion. We observed that the VMPSf membrane could reduce the number of adhered platelets without altering their spherical or elliptical shape. The PAR1 levels in VMPSf membranes were 7.4 MFI lower than those in PSf membranes, suggesting that this modified membrane can effectively inhibit platelet activation. Activated partial thromboplastin time (APTT, 5.3 s extension) and thrombin time (TT, 2.1 s extension) reflect good anticoagulant properties. Recalcification time (80.6 s extension) and fibrinogen adsorption (9.9 μg/cm2reduction) were related to antithrombotic properties. To determine the biosafety of VMPSf membranes, we investigated antianaphylactic and anti-inflammatory properties in vitro and acute toxicity in vivo, it was obvious that C3a and C5a had decreased to 9.6 and 0.8 ng/mL, respectively. The results indicated that the VMPSf membrane has potential for clinical application.