Laboratory of Ultrasound Imaging Drug, Department of Ultrasound, West China School of Medicine/West China Hospital, Sichuan University, Chengdu 610041, China; College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China.
Laboratory of Ultrasound Imaging Drug, Department of Ultrasound, West China School of Medicine/West China Hospital, Sichuan University, Chengdu 610041, China.
Int J Biol Macromol. 2019 Feb 1;122:784-792. doi: 10.1016/j.ijbiomac.2018.11.011. Epub 2018 Nov 3.
Heparin-like biomacromolecules (HepLBm), exhibiting similar chemical structure and biological properties to heparin, can be obtained by modifying either synthetic biopolymers or natural biomacromolecules with physical or chemical methods. In this work, a low-cost and biocompatible sodium alginate was chosen as a model biomacromolecule to design anticoagulant HepLBm with a similar sulfation degree to heparin. FTIR, H NMR, and element analysis data were used to confirm the chemical structure of HepLBm. Hemolysis tests, clotting time, complement activation, and contact activation tests were carried out to determine the in vitro anticoagulant activity of HepLBm. In addition, systematic studies of blood cell count, coagulation function, and histopathology were performed to demonstrate the in vivo anticoagulant activity and toxicity of HepLBm with SD rat experiments. Furthermore, a series of linear molecules containing carboxyl groups, sulfonic groups, and hydroxyl groups were selected and their clotting time was tested to provide a mechanism analysis for the excellent anticoagulant activity of HepLBm. With the excellent in vitro/in vivo anticoagulant activity, good biocompatibility, and low cost, the HepLBm synthesized in this work would have great potential for substitution of heparin in many application fields, such as the surface modification of biomedical devices, extracorporeal anticoagulants, and other clinical fields.
肝素类似生物大分子（HepLBm），通过物理或化学方法修饰合成生物聚合物或天然生物大分子，可以获得具有类似肝素化学结构和生物学性质的物质。在这项工作中，选择了一种低成本且生物相容的海藻酸钠作为模型生物大分子，设计了一种具有类似肝素硫酸化程度的抗凝 HepLBm。傅里叶变换红外光谱（FTIR）、核磁共振氢谱（H NMR）和元素分析数据用于确证 HepLBm 的化学结构。通过溶血试验、凝血时间、补体激活和接触激活试验来测定 HepLBm 的体外抗凝活性。此外，通过 SD 大鼠实验进行了血细胞计数、凝血功能和组织病理学的系统研究，以证明 HepLBm 的体内抗凝活性和毒性。进一步选择了一系列含有羧基、磺酸基和羟基的线性分子，并测试了它们的凝血时间，为 HepLBm 优异的抗凝活性提供了机制分析。由于具有优异的体外/体内抗凝活性、良好的生物相容性和低成本，本工作中合成的 HepLBm 在许多应用领域（如生物医学器械的表面修饰、体外抗凝剂等临床领域）替代肝素具有巨大的潜力。
