Abstract：
Acute lung injury (ALI) linked to sepsis has a high mortality rate, with limited treatment options available. In recent studies, medical ozone has shown promising results in alleviating inflammation and infection. Here, we aimed to evaluate the therapeutic potential of medical ozone in sepsis-induced ALI using a mouse model, measuring behavioral assessments, lung function, and blood flow. Western blot was used to quantify the levels of protein. In vitro, experiments on BMDM cells examine the impact of AMPK inhibitors and agonists on phagocytic activity. Results indicate that medical ozone can enhance the survival rate, ameliorate lung injury, and improve lung function and limb microcirculation in mice with ALI. Notably, it inhibits NETs formation, a crucial player in ALI development. Medical ozone also counteracts elevated TF, MMP-9, and IL-1β levels. In ALI mice, the effects of ozone are nullified and BMDMs exhibit impaired engulfment of NETs following Sr-a1 knockout. Under normal physiological conditions, the use of an AMPK antagonist produces similar effects to Sr-a1 knockout, significantly inhibiting the phagocytosis of NETs by BMDMs. On the contrary, AMPK agonists enhance this phagocytic process. In conclusion, medical ozone can alleviate sepsis-induced lung injury via the AMPK/SR-A1 pathway, thereby enhancing phagocytosis of NETs by macrophages.
摘要：
与脓毒症相关的急性肺损伤(ALI)具有很高的死亡率,有限的治疗选择。在最近的研究中,医用臭氧在减轻炎症和感染方面显示出有希望的结果。这里,我们旨在使用小鼠模型评估医用臭氧在脓毒症诱导的ALI中的治疗潜力，衡量行为评估，肺功能,和血液流动。蛋白质印迹用于定量蛋白质的水平。体外，BMDM细胞实验检查AMPK抑制剂和激动剂对吞噬活性的影响。结果表明，医用臭氧可以提高存活率，改善肺损伤，改善ALI小鼠的肺功能和肢体微循环。值得注意的是,它抑制了NET的形成，在ALI发展中至关重要的参与者。医用臭氧还可以抵消升高的TF，MMP-9和IL-1β水平。在ALI小鼠中,在Sr-a1敲除后，臭氧的影响无效，BMDM表现出NETs的吞噬受损。在正常生理条件下,使用AMPK拮抗剂产生与Sr-a1敲除相似的效果，显着抑制BMDMs对NETs的吞噬作用。相反，AMPK激动剂增强了这种吞噬过程。总之,医用臭氧可通过AMPK/SR-A1通路减轻脓毒症肺损伤，从而增强巨噬细胞对NETs的吞噬作用。
