Desflurane protects against liver ischemia/reperfusion injury via regulating miR-135b-5p

J Chin Med Assoc. 2021 Jan 1;84(1):38-45. doi: 10.1097/JCMA.0000000000000427.

Abstract

Background: A number of anesthetics have protective effect against ischemia-reperfusion (I/R) injury, including desflurane. But the function and molecular mechanism of desflurane in liver I/R injury have not been fully understood. The aim of this study was to investigate the effect of desflurane on liver I/R injury and further investigated the molecular mechanisms involving in miR-135b-5p.

Methods: The models of liver I/R injury in rats were established, and received desflurane treatment throughout the injury. Serum alanine transaminase (ALT) and aspartate transaminase (AST) were measured and compared between groups. H/R-induced cell model in L02 was established, and were treated with desflurane before hypoxia. Quantitative real-time polymerase chain reaction was performed to determine the expression of miR-135b-5p in different groups. The cell apoptosis was detected using flow cytometry assay. Western blot was used for the measurement of protein levels.

Results: I/R significantly increased serum levels of ALT and AST in rats, which were reversed by desflurane treatment. Desflurane also significantly attenuated the increase of cell apoptosis induced by I/R in both vivo and vitro. MiR-135b-5p significantly reversed the protective effect of desflurane against liver I/R injury. Additionally, Janus protein tyrosine kinase (JAK)2 was shown to be a target gene of miR-135b-5p, and miR-135b-5p overexpression significantly decreased the protein levels of p-JAK2, JAK2, p-STAT3.

Conclusion: Desflurane attenuated liver I/R injury through regulating miR-135b-5p, and JAK2 was the target gene of mIR-135b-5p. These findings provide references for further development of therapeutic strategies in liver injury.

MeSH terms

  • Animals
  • Cells, Cultured
  • Desflurane / therapeutic use*
  • Humans
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / physiology
  • Liver / blood supply*
  • Male
  • MicroRNAs / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control*
  • STAT Transcription Factors / physiology

Substances

  • MIRN135 microRNA, human
  • MIRN135 microRNA, rat
  • MicroRNAs
  • STAT Transcription Factors
  • Desflurane
  • Janus Kinase 2