Esketamine mitigates lung injury in COPD rat models under mechanical ventilation: An RNA-sequencing and bioinformatics analysis of serum exosome miRNA profiles.

Abstract

This study aims to investigate the protective effects of esketamine on lung injury in rat models of chronic obstructive pulmonary disease (COPD) under mechanical ventilation. The focus is on serum exosome miRNA profiles through RNA sequencing and bioinformatics analysis. Male Sprague-Dawley rats were categorized into four groups: Control (C), COPD model (M), COPD model + saline (MS), and COPD model + esketamine (MK). After inducing COPD and subjecting the animals to mechanical ventilation, lung structure, and respiratory function were evaluated. Serum exosomes were isolated for RNA sequencing to analyze differentially expressed miRNAs and their associated pathways. Intervention with esketamine significantly improved lung histology, reduced inflammation, and enhanced respiratory mechanics in the MK group compared to the other COPD groups. Peak airway pressure, wet-to-dry weight ratio, and lung permeability index significantly improved. Analysis of serum exosome miRNA revealed the downregulation of several miRNAs, including rno-miR-143-3p, rno-miR-130a-3p, rno-miR-505-5p, rno-miR-122-5p, rno-miR-145-5p, and rno-miR-1b. These miRNAs were linked to target genes involved in critical pathways such as TGF-beta, PI3K-Akt, mTOR, and Ras signaling. Gene Ontology (GO) analysis indicated significant enrichment in biological processes related to signal transduction, cellular stress response, and intracellular trafficking. Esketamine demonstrates significant potential to alleviate lung injury in COPD rat models subjected to mechanical ventilation, likely through modulating critical pathways related to inflammation, fibrosis, and cellular stress. Further research is needed to confirm these findings in clinical settings.