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小尺寸富勒醇纳米颗粒通过抑制凝血酶和 FXa 的活性来抑制血栓形成和血液凝固。

Small size fullerenol nanoparticles inhibit thrombosis and blood coagulation through inhibiting activities of thrombin and FXa.

机构信息

CAS Key Laboratory for Biomedical Effects of Nanomaterial & Nanosafety, Institute of High Energy Physics, Chinese Academy of Science (CAS), Beijing, China; University of Chinese Academy of sciences (UCAS), Beijing, China.

CAS Key Laboratory for Biomedical Effects of Nanomaterial & Nanosafety, Institute of High Energy Physics, Chinese Academy of Science (CAS), Beijing, China.

出版信息

Nanomedicine. 2018 Apr;14(3):929-939. doi: 10.1016/j.nano.2017.12.013. Epub 2018 Jan 6.

DOI:10.1016/j.nano.2017.12.013
PMID:29309909
Abstract

Thrombus is one of main causes of death in the world and also a vital trouble of biomaterials application in vivo. Recently, effect of fullerenol nanomaterials on anticoagulation was found in our research through extension of bleeding times in treated Sprague-Dawley rats via intravenous injection. Inhibiting of fullerenols on thrombosis was ascertained further by thromboembolism model. Effects of fullerenols on intrinsic and extrinsic pathway were distinct in prolonging activated partial thromboplastin time and prothrombin time, which supported that fullerenols induced defects in both pathways. Inhibited activities of activated coagulation factor X (FXa) and thrombin were verified by experiments in vitro and AutoDock Vina. The results suggest that fullerenols depending on small size and certainly surface property occupied the active domain of FXa and thrombin to block their activity; further, thrombosis was inhibited. This putative mechanism offers an insight into how fullerenol NPs were utilized further in biomedical applications.

摘要

血栓是世界范围内主要的死亡原因之一,也是生物材料体内应用的一个重要问题。最近,我们通过静脉注射处理过的 Sprague-Dawley 大鼠的出血时间延长,在研究中发现富勒醇纳米材料对抗凝的影响。通过血栓栓塞模型进一步证实了富勒醇对血栓形成的抑制作用。富勒醇在外源和内源途径上延长激活部分凝血活酶时间和凝血酶原时间的作用不同,这表明富勒醇诱导了两条途径的缺陷。通过体外实验和 AutoDock Vina 验证了富勒醇抑制活化凝血因子 X(FXa)和凝血酶的活性。结果表明,富勒醇凭借其较小的尺寸和确定的表面特性占据了 FXa 和凝血酶的活性部位,从而阻断了它们的活性;进一步抑制了血栓形成。这种假设的机制为富勒醇纳米粒子如何进一步应用于生物医学提供了一个深入的了解。

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