Development of A Novel Murine Model of Combined Radiation and Peripheral Tissue Trauma Injuries.
Development of A Novel Murine Model of Combined Radiation and Peripheral Tissue Trauma Injuries.
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DOI：
10.1667/rr14557.1
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发表时间：
2017-02
影响因子：
3.4
通讯作者：
Vujaskovic Z
中科院分区：
文献类型：
--
作者：
Antonic V;Jackson IL;Ganga G;Shea-Donohue T;Vujaskovic Z
在城市环境中引爆一枚10千吨级核弹将造成100万人以上的伤亡，其中大多数是复合伤。联合损伤，如外周组织创伤和辐射暴露，触发炎症事件，导致多器官功能障碍（MOD）和死亡，胃肠道（GI）和肺部受累起着至关重要的作用。本研究的目的是建立一种复合损伤的动物模型，外周组织创伤（TBX动物模型）结合全身照射与5%骨髓屏蔽（TBI/BM 5），以研究外周组织创伤是否有助于降低生存率。将雄性C57 BL/6 J小鼠暴露于TBX10%、辐射（TBI/BM 5）或联合损伤（TBX10% + TBI/BM 5）。进行实验以评估TBI/BM后第7天的死亡率5。在TBI/BM后第1、3、6或7天进行连续安乐死，以评估复合损伤中病理生理过程的时间过程。进行功能测试以评估肺功能和GI运动。收集肺和空肠的死后样本以评估组织损伤。结果表明，与TBX 10%或TBI/BM 5组相比，TBX 10%+ TBI/BM 5组的致死率更高，存活率更短（分别为第1天对第7天和第6天）。单独的TBI/BM 5对肺没有影响，但在第6天显著损害GI功能。正如预期的那样，在接受严重创伤（TBX 10%）的动物中，我们观察到前3天肺功能受损和GI转运延迟，这些影响在随后的时间点降低。与TBX10%和TBI/BM 5组相比，创伤联合放疗（TBX10% + TBI/BM 5）在24 h时显著增加了肺和GI功能的损害。组织学评价表明，与其他组相比，TBX10% + TBI/BM 5组的复合损伤造成了更大的肠组织损伤。我们在这里描述的第一个组合的组织创伤/辐射损伤模型，将允许进行机械研究，以确定新的治疗靶点，并作为一个平台，用于测试新的治疗干预措施。
Detonation of a 10-kiloton nuclear bomb in an urban setting would result in >1 million casualties, the majority of which would present with combined injuries. Combined injuries, such as peripheral tissue trauma and radiation exposure, trigger inflammatory events that lead to multiple organ dysfunction (MOD) and death, with gastrointestinal (GI) and pulmonary involvement playing crucial roles. The objective of this study was to develop an animal model of combined injuries, peripheral tissue trauma (TBX animal model) combined with total body irradiation with 5% bone marrow shielding (TBI/BM5) to investigate if peripheral tissue trauma contributes to reduced survival. Male C57BL/6J mice were exposed to TBX10%, irradiation (TBI/BM5), or combined injuries (TBX10% + TBI/BM5). Experiments were conducted to evaluate mortality at day 7 after TBI/BM5. Serial euthanasia was performed at day 1, 3 and 6 or 7 after TBI/BM5 to evaluate the time course of pathophysiologic processes in combined injuries. Functional tests were performed to assess pulmonary function and GI motility. Postmortem samples of lungs and jejunum were collected to assess tissue damage. Results indicated higher lethality and shorter survival in the TBX10% +T BI/BM5 group than in the TBX10% or TBI/BM5 groups (day 1 vs. day 7 and 6, respectively). TBI/BM5 alone had no effects on the lungs but significantly impaired GI function at day 6. As expected, in the animals that received severe trauma (TBX10%), we observed impairment in lung function and delay in GI transit in the first 3 days, effects that decreased at later time points. Trauma combined with radiation (TBX10% + TBI/BM5) significantly augmented impairment of the lung and GI function in comparison to TBX10% and TBI/BM5 groups at 24 h. Histologic evaluation indicated that combined injuries caused greater tissue damage in the intestines in TBX10% + TBI/BM5 group when compared to other groups. We describe here the first combined tissue trauma/radiation injury model that will allow conduction of mechanistic studies to identify new therapeutic targets and serve as a platform for testing novel therapeutic interventions.