Sevoflurane Alleviates Myocardial Ischemia/Reperfusion Injury by Targeting the circ_CDR1as/miR-671-5p/HMGA1 Axis

J Biochem Mol Toxicol. 2025 Jan;39(1):e70094. doi: 10.1002/jbt.70094.

Abstract

Sevoflurane (Sev) has a cardioprotective role in myocardial ischemia/reperfusion injury (MI/RI), but its mechanism has not been fully elucidated. This study aimed to investigate whether the circ_CDR1as/miR-671-5p/HMGA1 axis mediates the cardioprotective effect of Sev in MI/RI. Cardiomyocytes underwent hypoxia/reoxygenation (H/R) treatment was used to simulate MI/RI in vitro. H/R cardiomyocytes were then pretreated with Sev to explore the protective effect of Sev on H/R cells. The level of CDR1as/miR-671-5p/HMGA1 axis were detected by RT-qPCR. The proliferation and apoptosis of cardiomyocytes were detected by CCK-8 and flow cytometry. The levels of myocardial injury markers and inflammatory markers were detected by ELISA assay. Finally, the regulatory relationship between CDR1as and miR-671-5p/HMGA1 axis was verified by Dual-luciferase reporting and RNA pull-down assays. Sev Pretreatment can reduce the level of CDR1as and mitigate H/R-induced damage to cardiomyocytes. This Pretreatment lowers the levels of myocardial injury markers, oxidative stress markers, and pro-inflammatory factors in H/R-affected cardiomyocytes. However, CDR1as overexpression inhibits Sev's protective effect on H/R cardiomyocytes. At the molecular mechanism, we found that CDR1as mediates Sev's protective effect through the CDR1as/miR-671-5p/HMGA1 axis. CDR1as increases HMGA1 levels by sponging miR-671-5p, while high HMGA1 levels diminish Sev's protective effect. Sev plays a cardioprotective role in MI/RI by inhibiting the circ_CDR1as/miR-671-5p/HMGA1 axis.

Keywords: CDR1as/miR‐671‐5p/HMGA1 axis; inflammation; myocardial ischemia/reperfusion injury; oxidative stress; sevoflurane.

MeSH terms

  • Animals
  • Cell Line
  • HMGA1a Protein* / genetics
  • HMGA1a Protein* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Myocardial Reperfusion Injury* / drug therapy
  • Myocardial Reperfusion Injury* / genetics
  • Myocardial Reperfusion Injury* / metabolism
  • Myocardial Reperfusion Injury* / pathology
  • Myocardial Reperfusion Injury* / prevention & control
  • Myocytes, Cardiac* / drug effects
  • Myocytes, Cardiac* / metabolism
  • Myocytes, Cardiac* / pathology
  • RNA, Circular / genetics
  • RNA, Circular / metabolism
  • Rats
  • Sevoflurane* / pharmacology

Substances

  • Sevoflurane
  • MicroRNAs
  • HMGA1a Protein
  • RNA, Circular