Medical ozone alleviates acute lung injury by enhancing phagocytosis targeting NETs via AMPK/SR-A1 axis
Chenxiao Yan1
Yong Zhang2
Lai Jin3
Xiaojie Liu4
Xuexian Zhu3
Qifeng Li3
Yu Wang3
Liang Hu3
Xueming He5
Hongguang Bao6
Xia Zhu5
Qian Wang1
Wen-Tao Liu3
1.The Key Laboratory of Rare Metabolic Disease,Department of Biochemistry and Molecular Biology,the Key Laboratory of Human Functional Genomics of Jiangsu Province,Key Laboratory of Targeted Intervention of Cardiovascular Disease,Collaborative Innovation Center for Cardiovascular Disease Translational Medicine,Nanjing Medical University,Nanjing,Jiangsu 211166,China2.Department of Anesthesiology,Nanjing First Hospital,Nanjing Medical University,Nanjing,Jiangsu 210006,China;Jiangsu Key Laboratory of Neurodegeneration,Department of Pharmacology,Nanjing Medical University,Nanjing,Jiangsu 211166,China3.Jiangsu Key Laboratory of Neurodegeneration,Department of Pharmacology,Nanjing Medical University,Nanjing,Jiangsu 211166,China4.Jiangsu Key Laboratory of Neurodegeneration,Department of Pharmacology,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Department of Anesthesiology,the Affiliated Drum Tower Hospital,Medical School of Nanjing University,Nanjing,Jiangsu 210009,China5.Center for Clinical Research and Translational Medicine,Department of Anesthesiology,the Affiliated Lianyungang Oriental Hospital of Xuzhou Medical University,Lianyungang,Jiangsu 222042,China;Department of Anesthesiology,the Affiliated Lianyungang Oriental Hospital of Kangda College of Nanjing Medical University,Lianyungang,Jiangsu 222042,China6.Department of Anesthesiology,Nanjing First Hospital,Nanjing Medical University,Nanjing,Jiangsu 210006,China
摘要：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.
机标关键词：ampkaxisnetsacutealleviatesenhancinginjurylung
分类号：R563(呼吸系及胸部疾病)
论文发表日期：2024-11-30
在线出版日期：2026-03-31（本平台首次上网日期，不代表文献的发表时间）
页数：17( 中插5,569-584 )
英文信息