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。

結果 (中文) 3:

背景：急性大时致肺损伤的特点是炎性反应的变化，并进行纤维化病变发展的晚期阶段损伤。最终，随之而来将完成结构的消融，如果源炎症/纤维化介质和氧化应激是不会被删除或衰减。因此，本研究的目的是确定是否细胞外超氧化物歧化酶的过度表达（EC-SOD）小鼠的改善通过抑制活化的TGF和急性辐射损伤下调的信号转导通路Smad 3臂。方法：整个胸部辐射（单剂量15 Gy）送到EC-SOD转基因（XRT-TG）和野生型（XRT-WT）动物。小鼠牺牲在1天，1周，3，6，10和14周。呼吸率，右肺重量、总/白细胞分类计数，激活TGFbeta1和组成信号转导通路（Smad 3和P-SMAD 2 / 3）进行了评估确定肺损伤。结果：照射的野生型（XRT-WT）的动物表现出时间依赖性增加在呼吸速率和右肺重量，而这些参数在照射后、6、14、10和3周时显著增加（P＜0.05）（XRT-TG）转基因小鼠。的炎症反应，其特征在于主要由巨噬细胞浸润XRT-WT小鼠明显。急性炎症明显减轻（P＜0.05）在XRT-TG动物在1、3、6和14周.活性TGFbeta1和组件的信号转导的表达通路均显著降低（P＜0.05）在稍后的时间点XRT-TG vs.xrt-wt.结论：本研究表明，过度的EC-SOD具有保护抗逆转录致急性肺损伤。EC-SOD似乎工作，部分通过巨噬细胞的响应衰减和降低TGFbeta1激活与随后的纤维化转化生长因子β通路下调。