Department of Hematology, Xiangya Hemophilia Diagnosis and Treatment Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Macromol Biosci. 2024 Jun;24(6):e2300496. doi: 10.1002/mabi.202300496. Epub 2024 Mar 3.
The contact between the dialysis membrane and blood can induce oxidative stress and thrombosis, causing oxidative organ damage and impaired toxin clearance. To date, the selection of anticoagulants has focused on mechanisms inhibiting white, but not red (erythrocytes) thrombus formation. In the present study, polyethersulfone (PES) membranes are modified with the antioxidant drug tiopronin; the physicochemical properties and dialysis performance of the Tio-PES membranes are evaluated. The effects on erythrocyte thrombosis are evaluated in terms of erythrocyte morphology, prothrombotic properties (adhesion, aggregation, viscosity, sedimentation, and hemolysis), and fibrinogen (FIB)-erythrocyte interactions. The regular anticoagulant and antiplatelet properties are also assessed. Superoxide dismutase, malondialdehyde, plasma protein, and complement C3a are further determined. Finally, the biosafety of the Tio-PES membranes is evaluated both in vitro and in vivo. The Tio-PES membranes exhibit excellent physicochemical properties and improved dialysis performance. It is found that the Tio-PES membranes stabilize erythrocyte morphology, reduce erythrocyte prothrombotic properties, decrease FIB adsorption, and prevent red thrombus formation. In addition, the Tio-PES membranes exhibit excellent antioxidant properties and show biosafety in primary toxicity studies. Thus, Tio-PES membranes hold promise as novel, safe, and effective dialysis materials for potential clinical application.
透析膜与血液的接触会引起氧化应激和血栓形成，导致氧化器官损伤和毒素清除受损。迄今为止，抗凝剂的选择主要集中在抑制白细胞（但不包括红细胞）血栓形成的机制上。在本研究中，聚醚砜（PES）膜用抗氧化药物硫普罗宁进行修饰；评估了 Tio-PES 膜的物理化学性质和透析性能。从红细胞形态、促血栓形成特性（粘附、聚集、粘度、沉降和溶血）以及纤维蛋白原（FIB）-红细胞相互作用等方面评估了对红细胞血栓形成的影响。还评估了常规抗凝和抗血小板特性。进一步测定超氧化物歧化酶、丙二醛、血浆蛋白和补体 C3a。最后，在体外和体内评估了 Tio-PES 膜的生物安全性。Tio-PES 膜具有优异的物理化学性质和改善的透析性能。结果发现，Tio-PES 膜稳定红细胞形态，降低红细胞促血栓形成特性，减少 FIB 吸附，防止红细胞血栓形成。此外，Tio-PES 膜具有优异的抗氧化性能，在原发性毒性研究中表现出生物安全性。因此，Tio-PES 膜有望成为新型、安全、有效的透析材料，具有潜在的临床应用前景。
