DMPP attenuates lipopolysaccharide-induced lung injury by inhibiting glycocalyx degradation through activation of the cholinergic anti-inflammatory pathway.

Autor: Qi F; Department of Emergency Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.; Emergency Intensive Care Unit, Nantong First People's Hospital, 666 Shengli Road, Nantong, 226004, China., Duan C; Clinical Research Center, Nantong First People's Hospital, 666 Shengli Road, Nantong, 226004, China., Chen T; Clinical Research Center, Nantong First People's Hospital, 666 Shengli Road, Nantong, 226004, China., Li F; Emergency Intensive Care Unit, Nantong First People's Hospital, 666 Shengli Road, Nantong, 226004, China., Zhang J; Department of Emergency Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. zhangjso@njmu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of bioenergetics and biomembranes [J Bioenerg Biomembr] 2023 Dec; Vol. 55 (6), pp. 447-456. Date of Electronic Publication: 2023 Oct 18.
DOI: 10.1007/s10863-023-09989-0
Abstrakt: The study aimed to investigate the therapeutic potential of 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), an agonist of nicotinic acetylcholine receptor (nAChR), in treating acute lung injury (ALI) induced by lipopolysaccharide (LPS). A murine ALI model was developed utilizing intraperitoneal injection of LPS. We evaluated the therapeutic efficacy of DMPP treatment in LPS-induced lung injury using various approaches, including pathohistological evaluation, appraisal of pulmonary edema, and measurement of inflammatory cytokine levels and their associated pathways within lung tissues. The gene chip data of LPS-induced acute lung injury mice were retrieved from the Gene Expression Omnibus (GEO) database for gene differential expression analysis and Gene Set Enrichment Analysis (GSEA) analysis. The impact of DMPP on glycocalyx shedding was assessed by measuring the expression levels of syndecan-1 (SDC-1) and matrix metalloproteinase-9 (MMP-9). DMPP treatment significantly improved pathomorphological changes and pathological lung injury scores in the LPS-induced ALI mouse model. The genes expressed differentially in the LPS-induced ALI group in GSE2411 were found to be involved in multiple processes, including the NF-κB signaling pathway, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, as well as the JAK-STAT signaling pathway. DMPP treatment effectively downregulated pro-inflammatory cytokines, suppressed the NF-κB signaling pathway, and effectively restrained the LPS-induced upregulation of MMP-9 and shedding of syndecan-1, thereby contributing to the preservation of endothelial glycocalyx and attenuation of endothelial barrier dysfunction. The administration of DMPP has been shown to confer protection against LPS-induced acute lung injury via a cholinergic anti-inflammatory pathway, which effectively inhibits endothelial glycocalyx degradation.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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