Neutrophil membrane-engineered Panax ginseng root-derived exosomes loaded miRNA 182-5p targets NOX4/Drp-1/NLRP3 signal pathway to alleviate acute lung injury in sepsis: experimental studies

Int J Surg. 2024 Jan 1;110(1):72-86. doi: 10.1097/JS9.0000000000000789.

Abstract

Background: The purpose of this study was to prepare neutrophil membrane-engineered Panax ginseng root-derived exosomes (N-exo) and investigate the effects of N-exo microRNA (miRNA) 182-5p (N-exo-miRNA 182-5p) on acute lung injury (ALI) in sepsis.

Methods: Panax ginseng root-derived exosomes were separated by differential centrifugation. Neutrophil membrane engineering was performed on exo to obtain N-exo. miRNA182-5p was transmitted into N-exo by electroporation technology to obtain N-exo-miRNA 182-5p. LPS was used to establish an in-vivo and in-vitro model of ALI of sepsis to evaluate the anti-inflammatory effect of N-exo-miRNA 182-5p.

Results: The results of transmission electron microscope showed that exo was a double-layer membrane structure like a saucer. Nanoparticle size analysis showed that the average particle size of exo was 129.7 nm. Further, compared with exo, the level of miRNA182-5p was significantly increased in N-exo. The experimental results showed that N-exo-miRNA 182-5p significantly improved ALI via target regulation of NOX4/Drp-1/NLRP3 signal pathway in vivo and in vitro .

Conclusion: In conclusion, this study prepared a novel engineered exosome (N-exo and N-exo-miRNA 182-5p significantly improved ALI in sepsis via target regulation of NOX4/Drp-1/NLRP3 signal pathway, providing new ideas and methods for treatment of ALI in sepsis.

MeSH terms

  • Acute Lung Injury* / genetics
  • Acute Lung Injury* / metabolism
  • Acute Lung Injury* / therapy
  • Drugs, Chinese Herbal*
  • Exosomes* / genetics
  • Exosomes* / metabolism
  • Humans
  • MicroRNAs* / genetics
  • NADPH Oxidase 4 / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Neutrophils
  • Panax*
  • Plant Extracts*
  • Sepsis* / genetics
  • Sepsis* / therapy
  • Signal Transduction

Substances

  • MicroRNAs
  • Asian ginseng
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NOX4 protein, human
  • NADPH Oxidase 4
  • Mirn182 microRNA, human
  • Drugs, Chinese Herbal
  • Plant Extracts