BACKGROUND: Acute RT-induced damage

BACKGROUND: Acute RT-induced damage to the lung is characterized by inflammatory
changes, which proceed to the development of fibrotic lesions in the late phase
of injury. Ultimately, complete structural ablation will ensue, if the source of
inflammatory/fibrogenic mediators and oxidative stress is not removed or
attenuated. Therefore, the purpose of this study is to determine whether
overexpression of extracellular superoxide dismutase (EC-SOD) in mice ameliorates
acute radiation induced injury by inhibiting activation of TGFbeta1 and
downregulating the Smad 3 arm of its signal transduction pathway.
METHODS: Whole thorax radiation (single dose, 15 Gy) was delivered to EC-SOD
overexpressing transgenic (XRT-TG) and wild-type (XRT-WT) animals. Mice were
sacrificed at 1 day, 1 week, 3, 6, 10 and 14 weeks. Breathing rates, right lung
weights, total/differential leukocyte count, activated TGFbeta1 and components of
its signal transduction pathway (Smad 3 and p-Smad 2/3) were assessed to
determine lung injury.
RESULTS: Irradiated wild-type (XRT-WT) animals exhibited time dependent increase
in breathing rates and right lung weights, whereas these parameters were
significantly less increased (p < 0.05) at 3, 6, 10 and 14 weeks in irradiated
transgenic (XRT-TG) mice. An inflammatory response characterized predominantly by
macrophage infiltration was pronounced in XRT-WT mice. This acute inflammation
was significantly attenuated (p < 0.05) in XRT-TG animals at 1, 3, 6 and 14
weeks. Expression of activated TGFbeta1 and components of its signal transduction
pathway were significantly reduced (p < 0.05) at later time-points in XRT-TG vs.
XRT-WT.
CONCLUSION: This study shows that overexpression of EC-SOD confers protection
against RT-induced acute lung injury. EC-SOD appears to work, in part, via an
attenuation of the macrophage response and also decreases TGFbeta1 activation
with a subsequent downregulation of the profibrotic TGFbeta pathway.

結果 (中文) 1:

背景︰ 肺 RT 引起的急性损害特点是炎症进入肝纤维化病变进展的晚期阶段的变化伤害。最终，完整结构消融将紧随其后，如果的来源炎症/纤维化调解员和氧化应激不会删除或减毒。因此，本研究的目的是确定是否胞外超氧化物歧化酶 （EC-超氧化物歧化酶） 在小鼠中的过度表达变好急性辐射损伤通过抑制活化的 TGFbeta1 和降糖 Smad 3 臂及其信号转导通路。方法︰ 整个胸部辐射 （单剂量，15 Gy） 被送到 EC-超氧化物歧化酶超量表达转基因 (XRT TG) 和野生型 (XRT WT) 动物。老鼠牺牲在 1 天、 1 周、 3、 6、 10、 14 周。右肺呼吸率重量，共和差速白细胞计数，激活 TGFbeta1 及组成对评估及其信号转导通路 （Smad 3 和 p-Smad 2/3）确定肺损伤。结果︰ 辐照的野生型 (XRT WT) 动物展出时间依赖增加在呼吸率和右肺重量，而这些参数显著增加 (p < 0.05) 3，少 6、 10 和 14 周在辐照(XRT TG) 转基因的小鼠。炎症反应的主要特点巨噬细胞浸润明显 XRT WT 小鼠。发生急性炎症在 XRT TG 动物在 1、 3、 6 和 14 是大大减毒 (p < 0.05)周。表达的激活 TGFbeta1 和组件及其信号转导机制通路在以后的时间点在 XRT TG vs 显著减少 (p < 0.05)。XRT WT。结论︰ 本研究表明过量表达的 EC-超氧化物歧化酶赋予保护对 RT 诱导的急性肺损伤。EC-超氧化物歧化酶似乎在部分，通过工作衰减的巨噬细胞反应，也减少 TGFbeta1 激活促 TGFbeta 通路随后表达下调。