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质子辐照雪貂低凝血病发生机制的研究。

Mechanism of hypocoagulability in proton-irradiated ferrets.

机构信息

Department of Radiation Oncology, University of Pennsylvania , Philadelphia, PA.

出版信息

Int J Radiat Biol. 2013 Oct;89(10):823-31. doi: 10.3109/09553002.2013.802394. Epub 2013 Jun 10.

Abstract

PURPOSE

To determine the mechanism of proton radiation- induced coagulopathy.

MATERIAL AND METHODS

Ferrets were exposed to either solar particle event (SPE)-like proton radiation at a predetermined dose rate of 0.5 Gray (Gy) per hour (h) for a total dose of 0 or 1 Gy. Blood was collected pre- and post-irradiation for a complete blood cell count or a soluble fibrin concentration analysis, to determine whether coagulation activation had occurred. Tissue was stained with an anti-fibrinogen antibody to confirm the presence of fibrin in blood vessels.

RESULTS

SPE-like proton radiation exposure resulted in coagulation cascade activation, as determined by increased soluble fibrin concentration in blood from 0.7-2.4 at 3 h, and 9.9 soluble fibrin units (p < 0.05) at 24 h post-irradiation and fibrin clots in blood vessels of livers, lungs and kidneys from irradiated ferrets. In combination with this increase in fibrin clots, ferrets had increased prothrombin time and partial thromboplastin time values post-irradiation, which are representative of the extrinsic/intrinsic coagulation pathways. Platelet counts remained at pre-irradiation values over the course of 7 days, indicating that the observed effects were not platelet-related, but instead likely to be due to radiation-induced effects on secondary hemostasis. White blood cell (WBC) counts were reduced in a statistically significant manner from 24 h through the course of the seven-day experiment.

CONCLUSIONS

SPE-like proton radiation results in significant decreases in all WBC counts as well as activates secondary hemostasis; together, these data suggest severe risks to astronaut health from exposure to SPE radiation.

摘要

目的

确定质子辐射诱导性凝血病的机制。

材料和方法

用类似于太阳粒子事件(SPE)的质子辐射照射雪貂,剂量率为 0.5 Gray(Gy)/小时(h),总剂量为 0 或 1 Gy。在照射前后采集血液进行全血细胞计数或可溶性纤维蛋白浓度分析,以确定是否发生了凝血激活。用抗纤维蛋白原抗体对组织进行染色,以确认血管中存在纤维蛋白。

结果

SPE 样质子辐射暴露导致凝血级联激活,这可以通过照射后 3 小时血液中可溶性纤维蛋白浓度从 0.7-2.4 增加到 24 小时时的 9.9 可溶性纤维蛋白单位(p < 0.05)以及从照射的雪貂的肝脏、肺和肾脏血管中的纤维蛋白栓来确定。与纤维蛋白栓的增加相结合,雪貂在照射后出现了凝血酶原时间和部分促凝血酶原时间值增加,这代表了外源性/内源性凝血途径。血小板计数在 7 天的过程中保持在照射前的值,表明观察到的效应不是血小板相关的,而是可能由于辐射对二次止血的影响。白细胞(WBC)计数从 24 小时到七天实验的过程中显著减少。

结论

SPE 样质子辐射导致所有 WBC 计数显著减少,并激活二次止血;这些数据表明,宇航员暴露于 SPE 辐射会严重威胁健康。

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