Therapeutic effects and mechanisms of medical ozone on sepsis-associated kidney injury
10.11665/j.issn.1000-5048.2025040801
- VernacularTitle:医用臭氧对脓毒症肾损伤的治疗作用及其机制
- Author:
Yaqi LUAN
1
;
Xiaojie LIU
;
Changlin SUN
;
Wentao LIU
;
Lai JIN
;
Rong WANG
Author Information
1. 山东第一医科大学附属省立医院, 济南250117; 南京医科大学基础医学院, 南京211166
- Publication Type:Journal Article 期刊文章
- Keywords:
sepsis-associated kidney injury;
tissue factor-rich microparticles;
neutrophil extracellular traps;
scavenger receptor-A1;
medical ozone
- From:
Journal of China Pharmaceutical University
2025;56(5):601-612
- CountryChina
- Language:Chinese
-
Abstract:
This study investigated the therapeutic effects and mechanisms of medical ozone on sepsis- associated kidney injury (S-AKI) induced by lipopolysaccharide in mice. Using enzyme-linked immunosorbent assay, renal histopathological evaluation, detection of renal function biochemical indicators, immunofluorescence staining, and Western blot analysis, the effects of intraperitoneal injection of ozone on inflammation, coagulation, and renal tissue in mice were systematically detected.The results demonstrated that ozone treatment significantly reduced circulating levels of the specific markers (citrullinated histone H3 and myeloperoxidase-DNA complexes) from neutrophil extracellular traps (NETs) in S-AKI mice, with a suppression on inflammatory and tissue factor expression in renal tissue. Furthermore, ozone effectively improved microcirculation dysfunction, reduced tubular damage and interstitial inflammatory infiltration, thereby alleviating pathological changes of kidneys of S-AKI mice. Mechanistic studies revealed that ozone enhances phagocytic clearance of tissue factor-rich microparticles (TF-MPs) by activating the 5'-monophosphate-activated protein kinase (AMPK) / scavenger receptor (SR)-A1 signaling pathway in macrophages. In Sr-a1-/- mice, renoprotective effect of ozone was completely abolished, confirming the critical role of SR-A1 in this mechanism. In summary, this study demonstrates that medical ozone promotes macrophage clearance of TF-NETs complexes through the AMPK/SR-A1 signaling axis, exerting dual protective effects on mice through anti-inflammatory action and microcirculation improvement, which provides novel intervention targets and therapeutic strategies for S-AKI treatment.
