Dexmedetomidine alleviates myocardial ischemia-reperfusion injury by down-regulating miR-34b-3p to activate the Jagged1/Notch signaling pathway

Background: Myocardial ischemia/reperfusion (I/R) injury is a fatal event that usually occurs after reperfusion therapy for myocardial infarction. Dexmedetomidine (Dex) has been shown to be beneficial in the treatment of myocardial infarction, however, its underlying mechanism for regulating I/R injury is unclear.Methods: H9c2 cell and rat models of I/R injury were established via oxygen-glucose deprivation reoxygenation (OGD/R) and occlusion of the left anterior descending branch of coronary artery, respectively. Flow cytometry, MTT, or DHE assay detected cell activity, ROS, or apoptosis, respectively. The expression levels of miR-34b-3p and related mRNAs were determined using qRT-PCR. Related protein expression levels were detected by Western blotting and ELISA test. The interaction between miR-34b-3p and Jagged1 was assessed by dual luciferase re-porter and RIP assays. The morphology of cardiac tissue was examined by TTC, HE, and TUNEL labeling.Results: Dex markedly inhibited the inflammatory damage and apoptosis caused by OGD/R in H9c2 cells. MiR-34b-3p and Jagged1 levels were increased and decreased in myocardial I/R injury model, respectively, while Dex reversed this effect. Moreover, miR-34b-3p was firstly reported to directly bind and decrease Jagged1 expression, thereby inhibiting Notch signaling pathway. Transfection of agomiR-34b-3p or Jagged1 silencing eliminated Dex's defensive impact on OGD/R-induced cardiomyocytes damage. Dex relieved the myocardial I/R injury of rats via inhibiting miR-34b-3p and further activating Notch signaling pathway.Conclusion: Dex protected myocardium from I/R injury via suppressing miR-34b-3p to activate Jagged1-mediated Notch signaling pathway. Our findings revealed a novel mechanism underlying of Dex on myocardial I/R injury.

Automated summary

Dexmedetomidine protects myocardium from ischemia/reperfusion (I/R) injury by suppressing miR-34b-3p to activate Jagged1-mediated Notch signaling pathway. Our findings reveal a novel mechanism underlying the effects of Dex on myocardial I/R injury.