Blood：抑制血栓及炎症发生的小分子物质多聚磷酸盐被发现

近日，来自美国伊利诺伊大学的研究者通过研究鉴别出了一组小分子，其可以干扰一种化合物的活性，这种化合物可以开启血凝素的多种步骤，包括引发血管和动脉障碍，俗称为血栓。这种小分子可以通过阻塞多聚磷酸盐化合物，从而治疗血栓，相比目前市场上的药物作用效果更加显著一些。相关研究成果刊登于国际杂志Blood上。

血栓在血管的受损处形成，用来抑制血液的流失；有时候血栓可以完全阻塞动脉或者血管，而且其周围的组织也会受损，来自美国CDC的数据显示，每年有300，000到600，000的人会患上深度血管血栓。

有两种途径可以诱发血栓形成，如果一个人受伤了，其组织因子途径可以快速帮其止血，但是若该途径中的任何蛋白质缺失，那么就会出现血流不止的情况。相比较而言，当血液与人工化物质接触以后，机体接触途径就会被激活，尽管这种途径可可以诱发致病的血栓形成，但是该途径缺少蛋白质的个体也不会出现继续流血的情况，这两种途径最终会汇集起来形成一个机体共有的途径。

2006年，研究者发现，当多聚磷酸盐从血小板中释放出以后，就可以激活接触途径，由于接触途径对于损伤后血栓形成并不必要，因此干扰多聚磷酸盐并不会产生流血副作用。

研究者发现一系列的正电荷分子可以结合在负电荷的多聚磷酸盐分子上，就会抑制其诱发血栓形成的能力，通过将这些正电荷分子加入到血管和血浆中，研究者就可以测定其抑制血栓形成和炎症表现的效力。

同时研究者还检测了这些小分子在动脉、静脉血栓小鼠机体中的作用，结果显示，这些小分子可以阻止或降低血栓的形成及副作用的发生，相关研究由NIH提供资助。

编译自：New Way to Inhibit Blood Clotting and Inflammation

doi:10.1182/blood-2012-07-444935
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PMID:

Inhibition of polyphosphate as a novel strategy for preventing thrombosis and inflammation

Stephanie A. Smith1, Sharon H. Choi1, Julie N.R. Collins1, Richard J. Travers1, Brian C. Cooley2, and James H. Morrissey1,*

Inorganic polyphosphates are linear polymers of orthophosphate that modulate blood clotting and inflammation. Polyphosphate accumulates in infectious microorganisms and is secreted by activated platelets; long-chain polyphosphate in particular is an extremely potent initiator of the contact pathway, a limb of the clotting cascade important for thrombosis but dispensable for hemostasis. Polyphosphate inhibitors therefore might act as novel antithrombotic/anti-inflammatory agents with reduced bleeding side effects. Anti-polyphosphate antibodies are unlikely owing to polyphosphate's ubiquity and simple structure, and while phosphatases such as alkaline phosphatase can digest polyphosphate, they take time and may degrade other biologically active molecules. We now identify a panel of polyphosphate inhibitors, including cationic proteins, polymers and small molecules, and report their effectiveness in vitro and in vivo. We also compare their effectiveness against the procoagulant activity of RNA. Polyphosphate inhibitors were antithrombotic in mouse models of venous and arterial thrombosis, and blocked the inflammatory effect of polyphosphate injected intradermally in mice. This study provides proof of principle for polyphosphate inhibitors as antithrombotic/anti-inflammatory agents in vitro and in vivo, with a novel mode of action compared to conventional anticoagulants.

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