{"title":"医用臭氧通过 AMPK/SR-A1 轴增强针对 NET 的吞噬作用,从而缓解急性肺损伤。","authors":"Chenxiao Yan, Yong Zhang, Lai Jin, Xiaojie Liu, Xuexian Zhu, Qifeng Li, Yu Wang, Liang Hu, Xueming He, Hongguang Bao, Xia Zhu, Qian Wang, Wen-Tao Liu","doi":"10.7555/JBR.38.20240038","DOIUrl":null,"url":null,"abstract":"<p><p>Acute lung injury (ALI) linked to sepsis has a high mortality rate, with limited treatment options available. In recent studies, medical ozone has shown the potential to alleviate inflammation and infection. Here, we aimed to evaluate therapeutic potential of medical ozone in a mouse model of the sepsis-induced ALI by measuring behavioral assessments, lung function, and blood flow. Protein levels were quantified by Western blotting. <i>In vitro</i>, we performed experiments on bone marrow-derived macrophages (BMDMs) to investigate the effect of adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitors and agonists on their phagocytic activity. The results showed that medical ozone significantly improved the survival rate, ameliorated lung injury, and enhanced lung function and limb microcirculation in mice with ALI. Notably, medical ozone inhibited the formation of neutrophil extracellular traps (NETs), a crucial factor in the ALI development. Additionally, medical ozone counteracted the elevated levels of tissue factor, matrix metalloproteinase-9, and interleukin-1β. In the ALI mice, the effects of ozone were abolished, and BMDMs showed an impaired capacity to engulf NETs following the <i>Sr-a1</i> knockout. Under normal physiological conditions, the administration of an AMPK antagonist showed similar effects on the <i>Sr-a1</i> knockout, significantly inhibiting the phagocytosis of NETs by BMDMs. In contrast, AMPK agonists enhanced this phagocytic process. In conclusion, medical ozone may alleviate the sepsis-induced lung injury through the AMPK/SR-A1 pathway, thereby enhancing the phagocytosis of NETs by macrophages.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"569-584"},"PeriodicalIF":2.4000,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629159/pdf/","citationCount":"0","resultStr":"{\"title\":\"Medical ozone alleviates acute lung injury by enhancing phagocytosis targeting NETs <i>via</i> AMPK/SR-A1 axis.\",\"authors\":\"Chenxiao Yan, Yong Zhang, Lai Jin, Xiaojie Liu, Xuexian Zhu, Qifeng Li, Yu Wang, Liang Hu, Xueming He, Hongguang Bao, Xia Zhu, Qian Wang, Wen-Tao Liu\",\"doi\":\"10.7555/JBR.38.20240038\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Acute lung injury (ALI) linked to sepsis has a high mortality rate, with limited treatment options available. In recent studies, medical ozone has shown the potential to alleviate inflammation and infection. Here, we aimed to evaluate therapeutic potential of medical ozone in a mouse model of the sepsis-induced ALI by measuring behavioral assessments, lung function, and blood flow. Protein levels were quantified by Western blotting. <i>In vitro</i>, we performed experiments on bone marrow-derived macrophages (BMDMs) to investigate the effect of adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitors and agonists on their phagocytic activity. The results showed that medical ozone significantly improved the survival rate, ameliorated lung injury, and enhanced lung function and limb microcirculation in mice with ALI. Notably, medical ozone inhibited the formation of neutrophil extracellular traps (NETs), a crucial factor in the ALI development. Additionally, medical ozone counteracted the elevated levels of tissue factor, matrix metalloproteinase-9, and interleukin-1β. In the ALI mice, the effects of ozone were abolished, and BMDMs showed an impaired capacity to engulf NETs following the <i>Sr-a1</i> knockout. Under normal physiological conditions, the administration of an AMPK antagonist showed similar effects on the <i>Sr-a1</i> knockout, significantly inhibiting the phagocytosis of NETs by BMDMs. In contrast, AMPK agonists enhanced this phagocytic process. In conclusion, medical ozone may alleviate the sepsis-induced lung injury through the AMPK/SR-A1 pathway, thereby enhancing the phagocytosis of NETs by macrophages.</p>\",\"PeriodicalId\":15061,\"journal\":{\"name\":\"Journal of Biomedical Research\",\"volume\":\" \",\"pages\":\"569-584\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-05-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629159/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biomedical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.7555/JBR.38.20240038\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biomedical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7555/JBR.38.20240038","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
摘要
与败血症有关的急性肺损伤(ALI)死亡率很高,而可供选择的治疗方法却很有限。在最近的研究中,医用臭氧在缓解炎症和感染方面显示出了良好的效果。在这里,我们的目的是利用小鼠模型评估医用臭氧在败血症诱发的 ALI 中的治疗潜力,并测量其行为评估、肺功能和血流量。我们使用 Western 印迹来量化蛋白质水平。在体外,对 BMDM 细胞进行了实验,研究 AMPK 抑制剂和激动剂对吞噬活性的影响。结果表明,医用臭氧能提高 ALI 小鼠的存活率、改善肺损伤、改善肺功能和肢体微循环。值得注意的是,医用臭氧可抑制ALI发展过程中的关键因素--NETs的形成。医用臭氧还能抵消TF、MMP-9和IL-1β水平的升高。在 ALI 小鼠中,臭氧的作用被抵消,Sr-a1 基因敲除后,BMDMs 对 NETs 的吞噬能力受损。在正常生理条件下,使用 AMPK 拮抗剂会产生与 Sr-a1 基因敲除类似的效果,显著抑制 BMDMs 对 NETs 的吞噬。相反,AMPK 激动剂则会增强这种吞噬过程。总之,医用臭氧可通过 AMPK/SR-A1 通路缓解脓毒症诱发的肺损伤,从而增强巨噬细胞对 NETs 的吞噬作用。
Medical ozone alleviates acute lung injury by enhancing phagocytosis targeting NETs via AMPK/SR-A1 axis.
Acute lung injury (ALI) linked to sepsis has a high mortality rate, with limited treatment options available. In recent studies, medical ozone has shown the potential to alleviate inflammation and infection. Here, we aimed to evaluate therapeutic potential of medical ozone in a mouse model of the sepsis-induced ALI by measuring behavioral assessments, lung function, and blood flow. Protein levels were quantified by Western blotting. In vitro, we performed experiments on bone marrow-derived macrophages (BMDMs) to investigate the effect of adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitors and agonists on their phagocytic activity. The results showed that medical ozone significantly improved the survival rate, ameliorated lung injury, and enhanced lung function and limb microcirculation in mice with ALI. Notably, medical ozone inhibited the formation of neutrophil extracellular traps (NETs), a crucial factor in the ALI development. Additionally, medical ozone counteracted the elevated levels of tissue factor, matrix metalloproteinase-9, and interleukin-1β. In the ALI mice, the effects of ozone were abolished, and BMDMs showed an impaired capacity to engulf NETs following the Sr-a1 knockout. Under normal physiological conditions, the administration of an AMPK antagonist showed similar effects on the Sr-a1 knockout, significantly inhibiting the phagocytosis of NETs by BMDMs. In contrast, AMPK agonists enhanced this phagocytic process. In conclusion, medical ozone may alleviate the sepsis-induced lung injury through the AMPK/SR-A1 pathway, thereby enhancing the phagocytosis of NETs by macrophages.