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

In a rat model of chronic obstructive pulmonary disease (COPD) subjected to mechanical ventilation, esketamine reduced lung injury. Rats given esketamine showed improved lung structure, less inflammation, and better respiratory mechanics compared to untreated COPD rats. Measures including peak airway pressure, wet-to-dry lung weight ratio, and lung permeability all improved. Analysis of serum exosome microRNAs identified several that were downregulated after esketamine treatment, 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 regulate genes in pathways such as TGF-beta, PI3K-Akt, mTOR, and Ras signaling, which are involved in inflammation, fibrosis, and cellular stress. The findings suggest esketamine may protect against ventilation-induced lung injury in COPD.

Study at a glance

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.