Page 69 - 《中国药科大学学报》2025年第5期

学报
Journal of China Pharmaceutical University 2025, 56(5): 601 − 612 601

医用臭氧对脓毒症肾损伤的治疗作用及其机制

栾亚萁 ，刘晓杰 ，孙长霖 ，刘文涛 ，金 莱 ，王 荣 1*
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（ 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）
摘 要 以脂多糖诱导的小鼠脓毒症相关肾损伤（sepsis-associated kidney injury，S-AKI）模型，探究医用臭氧对 S-AKI 的治
疗作用及机制。利用酶联免疫吸附试验、肾脏组织病理学评估、肾功能生化指标检测、免疫荧光染色及 Western blot 蛋白印迹
分析等方法，系统检测腹腔注射臭氧对小鼠炎症，凝血和肾组织的影响。结果显示，臭氧治疗可降低 S-AKI 小鼠循环系统中
的中性粒细胞胞外诱捕网（NETs）的特异性标志物（瓜氨酸化组蛋白 H3 和髓过氧化物酶-DNA 复合物）水平，同时抑制肾
脏组织中炎症因子及组织因子的表达。此外，臭氧还能有效改善肾脏微循环障碍，减轻肾小管损伤和间质炎症浸润，从而缓
解 S-AKI 的病理进程。机制研究表明，臭氧通过激活 5'-一磷酸腺苷活化的蛋白激酶（AMPK）/A1 类清道夫受体（SR-
A1）信号通路，增强巨噬细胞对组织因子富集微粒（TF-MPs）的吞噬清除能力。在 Sr-a1 基因敲除小鼠中，臭氧的肾脏保护
作用被完全消除，证实了 SR-A1 在该保护机制中的关键作用。综上，医用臭氧通过 AMPK/SR-A1 信号轴促进巨噬细胞清除
TF-NETs 复合物，发挥抗炎和改善微循环的双重保护效应，本研究为 S-AKI 的治疗提供了新的干预靶点和治疗策略。
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
中图分类号 R965 文献标志码 A 文章编号 1000−5048(2025)05−0601−12
doi：10.11665/j.issn.1000−5048.2025040801

引用本文 栾亚萁，刘晓杰，孙长霖，等. 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.

Cite this article as: LUAN Yaqi, LIU Xiaojie, SUN Changlin, et al. Therapeutic effects and mechanisms of medical ozone on sepsis-associated
kidney injury[J]. J China Pharm Univ, 2025, 56(5): 601 − 612.

Therapeutic effects and mechanisms of medical ozone on sepsis-associated
kidney injury

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LUAN Yaqi , LIU Xiaojie , SUN Changlin , LIU Wentao , JIN Lai , WANG Rong 1*
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Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250117; School of Basic Medical Science,
Nanjing Medical University, Nanjing 211166, China
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

收稿日期 2025-04-08 * 通信作者 Tel：13791082272 E-mail：wrjlsd@126.com
基金项目 国家自然科学基金项目（No. 82271252，No.81971047）