Wound trauma increases radiation-induced mortality by activation of iNOS pathway and elevation of cytokine concentrations and bacterial infection.
Wound trauma increases radiation-induced mortality by activation of iNOS pathway and elevation of cytokine concentrations and bacterial infection.
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DOI：
10.1667/rr1892.1
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发表时间：
2010-03
影响因子：
3.4
通讯作者：
Ledney, G. David
中科院分区：
文献类型：
--
作者：
Kiang, Juliann G.;Jiao, Wan;Cary, Lynnette H.;Mog, Steven R.;Elliott, Thomas B.;Pellmar, Terry C.;Ledney, G. David
虽然已有文献证明，合并伤可增加辐射损伤的死亡率，但复合伤的分子机制尚不清楚。在这项研究中，小鼠暴露于γ辐射，然后是皮肤损伤。创伤加重了辐射致死率，LD50/30从9.65Gy值降至8.95Gy值。在9.75Gy射线照射和/或创伤后不同时间对小鼠回肠和皮肤进行组织病理学、诱导型一氧化氮合酶(INOS)和血清细胞因子的分析。在回肠，伤后3d绒毛明显缩短，伤后无明显变化，复合伤后绒毛宽度和肌层厚度明显减少。复合伤小鼠的皮肤细胞较少，愈合芽也比单独受伤的小鼠小。复合伤显著延迟创面闭合时间，也延长了皮肤和回肠iNOS蛋白水平的升高。INOS上调与转录因子的增加有关，包括核因子-κB和核因子-白介素6。IL-6的升高可能是由于IL-1β，−6、−8、−9、−10和−13、G-CSF、嗜酸性粒细胞趋化因子、干扰素-γ、单核细胞趋化蛋白-1、α和β等细胞因子的增加所致。复合损伤导致心脏和肝脏血液中细菌的早期检测，而单独辐射导致较晚的细菌检测；只有在单独损伤后才会发生一过性菌血症。结果提示，复合伤引起的iNOS、细胞因子和细菌感染的增强可能是导致死亡的原因之一。抑制这些反应的药物可能被证明对复合损伤具有治疗作用，并可能降低相关死亡率。
Although it is documented that concurrent wounding increases mortality from radiation injury, the molecular mechanism of combined injury is unknown. In this study, mice were exposed to γ radiation followed by skin wounding. Wound trauma exacerbated radiation-induced mortality, reducing the LD50/30 from 9.65 Gy to 8.95 Gy. Analyses of histopathology, inducible nitric oxide synthase (iNOS), and serum cytokines were performed on mouse ileum and skin at various times after 9.75 Gy and/or wounding. In the ileum, the villi were significantly shortened 3 days postirradiation but not after wounding; combined injury resulted in decreased villus width and tunica muscularis thickness. The skin of mice subjected to combined injury was less cellular and had a smaller healing bud than the skin of mice subjected to wounding alone. Combined injury significantly delayed wound closure times; it also prolonged the increased levels of iNOS protein in the skin and ileum. iNOS up-regulation was correlated with increases in transcription factors, including NF-κB and NF-IL6. The increase in NF-IL6 may be due to increases in cytokines, including IL-1β, −6, −8, −9, −10 and −13, G-CSF, eotaxin, INF-γ, MCP-1, MIP-1α and MIP-1β. Combined injury resulted in early detection of bacteria in the blood of the heart and liver, whereas radiation alone resulted in later detection of bacteria; only a transient bacteremia occurred after wounding alone. Results suggest that enhancement of iNOS, cytokines and bacterial infection triggered by combined injury may contribute to mortality. Agents that inhibit these responses may prove to be therapeutic for combined injury and may reduce related mortality.