Wang PengCheng, Zhao QinYao, Zhu XiaoFang, Cao ShuangJiao, Williams John P, An Jianxiong
Laboratory of Anesthesia and Critical Care Medicine in Colleges and Universities of Shandong Province, School of Anesthesiology, Shandong Second Medical University, Weifang, Shandong, China.
Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Shock. 2025 Mar 1;63(3):487-494. doi: 10.1097/SHK.0000000000002525. Epub 2024 Dec 4.
Background: Acute lung injury (ALI) is a common respiratory emergency with high incidence and mortality. Among its main pathologic mechanisms is the rapid and intense inflammatory response. Ozone is a naturally occurring compound and is known for its properties as an oxidizing agent. Ozone therapy is the clinical application of a mixture of ozone (O 3 ) and oxygen, used within nontoxic, safe concentrations. It could be used for the treatment of several diseases. Ozone rectal insufflation (O 3 -RI) is a treatment in which medical O 3 is introduced into the rectum to treat and prevent disease. Although O 3 therapy exerts anti-inflammatory effects, its function in ALI remains unclear. The aim of this study was to preliminarily investigate the role and function of O 3 -RI in ALI. Methods: A mouse model of ALI was established by intratracheal administration of LPS. O 3 -RI was administered 4 h following the modeling procedure. Lung histopathology, lung wet/dry ratio, protein content in bronchoalveolar lavage fluid (BALF), and myeloperoxidase activity in lung tissues, as well as the number of inflammatory cells and inflammatory cytokines in BALF, were assessed. The expression levels of NOD-like receptor thermal protein domain associated protein (NLRP3)/apoptosis-associated speck-like protein (ASC)/caspase-1 axis-related proteins in lung tissues were examined by real-time fluorescence quantitative polymerase chain reaction and Western blotting. Results: Ozone therapy reduced the wet/dry ratio of lung tissue and total protein content in BALF and attenuated lung edema and microvascular leakage in ALI mice. Ozone therapy reduced the myeloperoxidase content in the lung tissue, the number of inflammatory cells, and the content of inflammatory cytokines in BALF and attenuated lung tissue inflammation in mice with ALI. Ozone therapy ameliorated lung tissue morphological damage in ALI mice. Ozone therapy downregulated the expression of NLRP3/ASC/caspase-1 axis-related proteins. Conclusion: Ozone therapy attenuated LPS-induced ALI in mice, possibly by inhibiting NLRP3/ASC/caspase-1 axis. Ozone therapy is a valuable potential therapeutic modality for ALI.
急性肺损伤（ALI）是一种常见的呼吸系统急症，发病率和死亡率都很高。其主要病理机制之一是快速而强烈的炎症反应。臭氧是一种天然存在的化合物，以其氧化剂特性而闻名。臭氧疗法是将臭氧（O₃）和氧气的混合物在无毒、安全的浓度范围内进行临床应用。它可用于治疗多种疾病。臭氧直肠注入（O₃-RI）是一种将医用臭氧引入直肠以治疗和预防疾病的疗法。尽管臭氧疗法具有抗炎作用，但其在ALI中的作用仍不清楚。本研究的目的是初步探讨O₃-RI在ALI中的作用和功能。方法：通过气管内注射脂多糖建立ALI小鼠模型。在建模后4小时给予O₃-RI。评估肺组织病理学、肺湿/干比、支气管肺泡灌洗液（BALF）中的蛋白质含量、肺组织中的髓过氧化物酶活性，以及BALF中的炎症细胞数量和炎症细胞因子。通过实时荧光定量聚合酶链反应和蛋白质免疫印迹法检测肺组织中NOD样受体热蛋白结构域相关蛋白（NLRP3）/凋亡相关斑点样蛋白（ASC）/半胱天冬酶-1轴相关蛋白的表达水平。结果：臭氧疗法降低了肺组织的湿/干比和BALF中的总蛋白含量，并减轻了ALI小鼠的肺水肿和微血管渗漏。臭氧疗法降低了肺组织中的髓过氧化物酶含量、炎症细胞数量以及BALF中的炎症细胞因子含量，并减轻了ALI小鼠的肺组织炎症。臭氧疗法改善了ALI小鼠的肺组织形态学损伤。臭氧疗法下调了NLRP3/ASC/半胱天冬酶-1轴相关蛋白的表达。结论：臭氧疗法可能通过抑制NLRP3/ASC/半胱天冬酶-1轴减轻脂多糖诱导的小鼠ALI。臭氧疗法是一种对ALI有潜在价值的治疗方式。
