: Acute lung injury (ALI), a common cause of morbidity and mortality in intensive care units, results from either direct intra-alveolar injury or indirect injury following systemic inflammation and oxidative stress. Adequate tissue oxygenation often requires additional supplemental oxygen. However, hyperoxia causes lung injury and pathological changes. Notably, preclinical data suggest that aspirin modulates numerous platelet-mediated processes involved in ALI development and resolution. Our previous study suggested that prehospital aspirin use reduced the risk of ALI in critically ill patients. This research uses an in vivo imaging system (IVIS) to investigate the mechanisms of aspirin's anti-inflammatory and antioxidant effects on hyperoxia-induced ALI in nuclear factor κB (NF-κB)-luciferase transgenic mice. To define mechanisms through which NF-κB causes disease, we developed transgenic mice that express luciferase under the control of NF-κB, enabling real-time in vivo imaging of NF-κB activity in intact animals. An NF-κB-dependent bioluminescent signal was used in transgenic mice carrying the luciferase genes to monitor the anti-inflammatory effects of aspirin. These results demonstrated that pretreatment with aspirin reduced luciferase expression, indicating that aspirin reduces NF-κB activation. In addition, aspirin reduced reactive oxygen species expression, the number of macrophages, neutrophil infiltration and lung edema compared with treatment with only hyperoxia treatment. In addition, we demonstrated that pretreatment with aspirin significantly reduced the protein levels of phosphorylated protein kinase B, NF-κB and tumor necrosis factor α in NF-κB-luciferase+/+ transgenic mice. Thus, the effects of aspirin on the anti-inflammatory response and reactive oxygen species suppressive are hypothesized to occur through the NF-κB signaling pathway. This study demonstrated that aspirin exerts a protective effect for hyperoxia-induced lung injury and thus is currently the drug conventionally used for hyperoxia-induced lung injury.

中文翻译：

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通过阿司匹林预处理抑制炎症和活性氧，以治疗高氧诱导的NF-κB-荧光素酶诱导的转基因小鼠急性肺损伤。

：急性肺损伤（ALI）是重症监护病房发病和死亡的常见原因，是由于直接肺泡内损伤或全身性炎症和氧化应激后的间接损伤所致。充足的组织氧合经常需要额外的补充氧。但是，高氧会引起肺损伤和病理变化。值得注意的是，临床前数据表明阿司匹林可调节参与ALI发育和分解的许多血小板介导的过程。我们先前的研究表明，院前服用阿司匹林可降低危重患者发生ALI的风险。这项研究使用体内成像系统（IVIS）来研究阿司匹林对核因子κB（NF-κB）-荧光素酶转基因小鼠高氧诱导的ALI的抗炎和抗氧化作用的机制。为了确定NF-κB引起疾病的机制，我们开发了在NF-κB的控制下表达荧光素酶的转基因小鼠，从而可以对完整动物中的NF-κB活性进行实时体内成像。在携带荧光素酶基因的转基因小鼠中使用了依赖于NF-κB的生物发光信号来监测阿司匹林的抗炎作用。这些结果表明，用阿司匹林预处理可降低荧光素酶表达，表明阿司匹林可降低NF-κB活化。此外，与仅高氧治疗相比，阿司匹林降低了活性氧的表达，巨噬细胞数量，中性粒细胞浸润和肺水肿。此外，我们证明了阿司匹林预处理可显着降低磷酸化蛋白激酶B的蛋白水平，NF-κB-萤光素酶+ / +转基因小鼠的NF-κB和肿瘤坏死因子α。因此，推测阿司匹林对抗炎反应和抑制活性氧的作用是通过NF-κB信号传导途径发生的。这项研究证明阿司匹林对高氧引起的肺损伤具有保护作用，因此目前是常规用于高氧引起的肺损伤的药物。