Korean J Physiol Pharmacol 2024; 28(6): 549-558
Published online November 1, 2024 https://doi.org/10.4196/kjpp.2024.28.6.549
Copyright © Korean J Physiol Pharmacol.
Lingling Zhen1,#, Mingtong Hou2,3,#, and Shengbao Wang2,3,*
1Intensive Care Unit, Lanzhou University Second Hospital, Lanzhou University, 2The Second Clinical Medical School, Lanzhou University, 3Emergency Center, Lanzhou University Second Hospital, Lanzhou University, Lanzhou 730030, Gansu, China
Correspondence to:Shengbao Wang
E-mail: wangshengbao@lzu.edu.cn
#These authors contributed equally to this work.
Author contributions: This manuscript was written by L.Z., M.H., and S.W. L.Z. worked independently on the research design and data analysis. M.H. took the lead in writing the manuscript, S.W. proofread all drafts. M.H. and S.W. gave first instructions for the paper, and L.Z. objectively proofread the manuscript.
Sepsis triggers a systemic inflammatory response that can lead to acute lung injury (ALI). Salidroside (SAL) has many pharmacological activities such as antiinflammatory and anti-oxidation. The objective of the study was to explore the mechanism of SAL on ALI caused by sepsis. A model of ALI in septic mice was established by cecal ligation and puncture. Following SAL treatment, the effect of SAL on the ferroptosis pathway in mice was analyzed. The pathological damage of lung tissue, the levels of inflammatory factors and apoptosis in bronchoalveolar lavage fluid (BALF) of mice were evaluated, and the changes of gene expression level and metabolite content abundance were explored by combining transcriptomics and metabolomics analysis. The effect of SAL on ferroptosis in mice with lung injury was observed by intraperitoneal injection of ferroptosis activator Erastin or ferroptosis inhibitor Ferrostatin-1 to promote or inhibit ferroptosis in mice. SAL significantly alleviated the pathological damage of lung tissue, decreased the number of TUNEL positive cells and the levels of TNF-α, IL-1β, IL-6 in BALF, and increased the level of IL- 10 in lung injury mice. Moreover, the Fe2+ content and malondialdehyde decreased significantly, the reactive oxygen species and glutathione content increased significantly, and the arachidonic acid metabolites 20-hydroxyeicosatetraenoic acid (20- HETE), (5Z, 8Z, 10E, 14Z)-12-Oxoeicosa-5,8,10,14-tetraenoic acid (12-OxOETE), (5Z, 8Z, 10E, 14Z)-(12S)-12-Hydroxyeicosa-5,8,10,14-tetraenoic acid (12(S)-HETE), (5Z, 8Z, 14Z)-11,12-Dihydroxyeicosa-5,8,14-trienoic acid (11,12-DHET), (5Z, 11Z, 14Z)-8,9- Dihydroxyeicosa-5,11,14-trienoic acid, Leukotriene B4, Leukotriene D4 were significantly up-regulated after SAL treatment. Salidroside alleviates ALI caused by sepsis by inhibiting ferroptosis.
Keywords: Acute lung injury, Arachidonic acid, Ferroptosis, Lipid metabolism, Rhodioloside, Sepsis
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