PDF(Pubmed)
Abstract：
Thromboembolic conditions are the most common cause of death in developed countries. Anticoagulant therapy is the treatment of choice, and heparinoids and warfarin are the most adopted drugs. Sulphated polysaccharides extracted from marine organisms have been demonstrated to be effective alternatives, blocking thrombus formation by inhibiting some factors involved in the coagulation cascade. In this study, four acidic glycan fractions from the marine sponge Sarcotragus spinosulus were purified by anion-exchange chromatography, and their anticoagulant properties were investigated through APTT and PT assays and compared with both standard glycosaminoglycans and holothurian sulphated polysaccharides. Moreover, their topographic localization was assessed through histological analysis, and their cytocompatibility was tested on a human fibroblast cell line. A positive correlation between the amount of acid glycans and the inhibitory effect towards both the intrinsic and extrinsic coagulation pathways was observed. The most effective anticoagulant activity was shown by a highly charged fraction, which accounted for almost half (about 40%) of the total hexuronate-containing polysaccharides. Its preliminary structural characterization, performed through infrared spectroscopy and nuclear magnetic resonance, suggested that it may consist of a fucosylated chondroitin sulphate, whose unique structure may be responsible for the anticoagulant activity reported herein for the first time.
摘要：
血栓栓塞疾病是发达国家最常见的死亡原因。抗凝治疗是首选的治疗方法，类肝素和华法林是最常用的药物。从海洋生物中提取的硫酸多糖已被证明是有效的替代品，通过抑制凝血级联反应中的一些因素来阻断血栓形成。在这项研究中,通过阴离子交换色谱纯化了来自海绵状沙棘的四个酸性聚糖级分，并通过APTT和PT测定研究了它们的抗凝血特性，并与标准糖胺聚糖和霍耳硫酸多糖进行了比较。此外，通过组织学分析评估了它们的地形定位，并在人成纤维细胞系上测试了它们的细胞相容性。观察到酸性聚糖的量与对内源性和外源性凝血途径的抑制作用之间呈正相关。高电荷部分显示出最有效的抗凝血活性，几乎占含己糖醛酸盐多糖总量的一半（约40％）。其初步结构表征,通过红外光谱和核磁共振，建议它可能由岩藻糖基化的硫酸软骨素组成，其独特的结构可能是本文首次报道的抗凝血活性的原因。
