Prevention and mitigation of acute death of mice after abdominal irradiation by the antioxidant N-acetyl-cysteine (NAC).
Prevention and mitigation of acute death of mice after abdominal irradiation by the antioxidant N-acetyl-cysteine (NAC).
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DOI：
10.1667/rr2030.1
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发表时间：
2010-05
影响因子：
3.4
通讯作者：
Corry PM
中科院分区：
文献类型：
--
作者：
Jia D;Koonce NA;Griffin RJ;Jackson C;Corry PM
胃肠道（GI）损伤是全身暴露于大剂量电离辐射后急性死亡的主要原因，但GI死亡的细胞和分子解释仍然不确定。为了解决这个问题，我们开发了一种小鼠腹部照射模型。用单剂量X射线照射小鼠腹部，每天s.c.注射N-乙酰基-L-半胱氨酸（NAC）或赋形剂7天，从照射前4小时或照射后2小时开始，并监测长达30天。分别地，在照射后6天测定来自每组的小鼠的骨髓活性氧（ROS）、骨髓基质细胞的离体集落形成和十二指肠的组织学变化。腹部照射引起剂量依赖性体重减轻和死亡。辐射诱导的急性死亡之前，不仅大量损失的十二指肠绒毛，而且，令人惊讶的是，远位抑制基质细胞和ROS在未照射的骨髓中的升高。NAC减少了这些辐射诱导的变化，并将10天和30天的存活率提高到>50%，而赋形剂治疗对照组的存活率<5%。我们的数据建立了一个中心的作用，骨髓活性氧的远位刺激在小鼠腹部照射后的急性死亡。
Gastrointestinal (GI) injury is a major cause of acute death after total-body exposure to large doses of ionizing radiation, but the cellular and molecular explanations for GI death remain dubious. To address this issue, we developed a murine abdominal irradiation model. Mice were irradiated with a single dose of X rays to the abdomen, treated with daily s.c. injection of N-acetyl-l-cysteine (NAC) or vehicle for 7 days starting either 4 h before or 2 h after irradiation, and monitored for up to 30 days. Separately, mice from each group were assayed 6 days after irradiation for bone marrow reactive oxygen species (ROS), ex vivo colony formation of bone marrow stromal cells, and histological changes in the duodenum. Irradiation of the abdomen caused dose-dependent weight loss and mortality. Radiation-induced acute death was preceded not only by a massive loss of duodenal villi but also, surprisingly, abscopal suppression of stromal cells and elevation of ROS in the nonirradiated bone marrow. NAC diminished these radiation-induced changes and improved 10- and 30-day survival rates to >50% compared with <5% in vehicle-treated controls. Our data establish a central role for abscopal stimulation of bone marrow ROS in acute death in mice after abdominal irradiation.