中国药科大学学报2025,Vol.56Issue(5):601-612,12.DOI:10.11665/j.issn.1000-5048.2025040801
医用臭氧对脓毒症肾损伤的治疗作用及其机制
Therapeutic effects and mechanisms of medical ozone on sepsis-associated kidney injury
摘要
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.关键词
脓毒症相关肾损伤/富含组织因子的微粒/中性粒细胞胞外诱捕网/清道夫受体A1/医用臭氧Key words
sepsis-associated kidney injury/tissue factor-rich microparticles/neutrophil extracellular traps/scavenger receptor-A1/medical ozone分类
医药卫生引用本文复制引用
栾亚萁,刘晓杰,孙长霖,刘文涛,金莱,王荣..医用臭氧对脓毒症肾损伤的治疗作用及其机制[J].中国药科大学学报,2025,56(5):601-612,12.基金项目
国家自然科学基金项目(No.82271252,No.81971047) This study was supported by the National Natural Science Foundation of China(No.82271252,No.81971047) (No.82271252,No.81971047)