Isoflurane Alleviates Myocardial Injury Induced by Hypoxia/Reoxygenation by Regulating miR-18a-5p

Cardiovasc Toxicol. 2021 Oct;21(10):800-807. doi: 10.1007/s12012-021-09670-1. Epub 2021 Jun 28.

Abstract

The protective effect and mechanism of isoflurane on myocardial injury was investigated by constructing in vitro hypoxia/reoxygenation (HR) cell model. HR cell models were established in vitro and treated with isoflurane (ISO). qRT-PCR was used to detect the relative expression of miR-18a-5p. CCK-8 kit and flow cytometry were performed to evaluate cell proliferation and apoptosis. The myocardial injury related markers, such as Cκ-MB, cTnI and LDH were detected by ELISA. Luciferase reporter gene assay was used to verify the interaction between miR-18a-5p and target genes. The expression of miR-18a-5p was significantly increased in hypoxic cardiomyocytes compared with control group (P < 0.001). Meanwhile, cardiomyocytes in the HR group showed inhibition of proliferation, a significant increase in cell apoptosis and in myocardial injury indicators, such as Cκ-MB, cTnI and LDH (P < 0.001). However, 1% ISO treatment alleviated myocardial cell injury induced by HR. Transfection of miR-18a-5p under ISO reduced the protective effect of 1% ISO against myocardial cell damage. Luciferase report gene assay confirmed that CCND2 might be the target gene of miR-18a-5p. In the in vitro cell model of myocardium, ISO alleviated cardiomyocyte injury caused by hypoxia/reoxygenation by down-regulating the expression of miR-18a-5p.

Keywords: Hypoxia/reoxygenation; Isoflurane; MiR-18a-5p; Myocardial injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Hypoxia
  • Cell Line
  • Cell Proliferation / drug effects*
  • Cyclin D2 / genetics
  • Cyclin D2 / metabolism
  • Down-Regulation
  • Isoflurane / pharmacology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • 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
  • Rats

Substances

  • Ccnd2 protein, rat
  • Cyclin D2
  • MIRN18 microRNA, rat
  • MicroRNAs
  • Isoflurane