Kiang Juliann G, Smith Joan T, Anderson Marsha N, Swift Joshua M, Christensen Christine L, Gupta Paridhi, Balakathiresan Nagaraja, Maheshwari Radha K
Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America; Department of Radiation Biology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
PLoS One. 2015 Sep 30;10(9):e0139271. doi: 10.1371/journal.pone.0139271. eCollection 2015.
Exposure to high-dose radiation results in detrimental effects on survival. The effects of combined trauma, such as radiation in combination with hemorrhage, the typical injury of victims exposed to a radiation blast, on survival and hematopoietic effects have yet to be understood. The purpose of this study was to evaluate the effects of radiation injury (RI) combined with hemorrhage (i.e., combined injury, CI) on survival and hematopoietic effects, and to investigate whether hemorrhage (Hemo) enhanced RI-induced mortality and hematopoietic syndrome. Male CD2F1 mice (10 weeks old) were given one single exposure of γ- radiation (60Co) at various doses (0.6 Gy/min). Within 2 hr after RI, animals under anesthesia were bled 0% (Sham) or 20% (Hemo) of total blood volume via the submandibular vein. In these mice, Hemo reduced the LD50/30 for 30-day survival from 9.1 Gy (RI) to 8.75 Gy (CI) with a DMF of 1.046. RI resulted in leukocytopenia, thrombopenia, erythropenia, and bone marrow cell depletion, but decreased the caspase-3 activation response. RI increased IL-1β, IL-6, IL-17A, and TNF-α concentrations in serum, bone marrow, ileum, spleen, and kidney. Some of these adverse alterations were magnified by CI. Erythropoietin production was increased in kidney and blood more after CI than RI. Furthermore, CI altered the global miRNAs expression in kidney and the ingenuity pathway analysis showed that miRNAs viz., let-7e, miR-30e and miR-29b that were associated with hematopoiesis and inflammation. This study provides preliminary evidence that non-lethal Hemo exacerbates RI-induced mortality and cell losses associated with high-dose γ-radiation. We identified some of the initial changes occurring due to CI which may have facilitated in worsening the injury and hampering the recovery of animals ultimately resulting in higher mortality.
暴露于高剂量辐射会对生存产生有害影响。联合创伤（如辐射与出血相结合，这是辐射爆炸受害者的典型损伤）对生存和造血的影响尚未明确。本研究的目的是评估辐射损伤（RI）合并出血（即复合损伤，CI）对生存和造血的影响，并研究出血（Hemo）是否会增强RI诱导的死亡率和造血综合征。雄性CD2F1小鼠（10周龄）接受单次不同剂量（0.6 Gy/分钟）的γ射线（60Co）照射。在RI后2小时内，对麻醉状态下的动物通过下颌下静脉放血，放血量为总血量的0%（假手术组）或20%（出血组）。在这些小鼠中，出血使30天生存的半数致死剂量（LD50/30）从9.1 Gy（RI组）降至8.75 Gy（CI组），剂量减低系数（DMF）为1.046。RI导致白细胞减少、血小板减少、红细胞减少和骨髓细胞耗竭，但降低了半胱天冬酶-3激活反应。RI使血清、骨髓、回肠、脾脏和肾脏中的白细胞介素-1β、白细胞介素-6、白细胞介素-17A和肿瘤坏死因子-α浓度升高。CI使其中一些不良改变加剧。CI后肾脏和血液中促红细胞生成素的产生比RI后增加得更多。此外，CI改变了肾脏中整体微小RNA（miRNA）的表达， Ingenuity通路分析显示，与造血和炎症相关的miRNA，即let-7e、miR-30e和miR-29b。本研究提供了初步证据，表明非致死性出血会加剧RI诱导的死亡率以及与高剂量γ射线相关的细胞损失。我们确定了CI导致的一些初始变化，这些变化可能促使损伤恶化并阻碍动物恢复，最终导致更高的死亡率。
