Dexmedetomidine improves myocardial ischemia-reperfusion injury by increasing autophagy via PINK1/PRKN pathway
1Department of Anesthesiology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430014 Wuhan, Hubei, China
2Department of Cardiology, Wenzhou Central Hospital, 325000 Wenzhou, Zhejiang, China
DOI: 10.22514/sv.2022.061 Vol.18,Issue 5,September 2022 pp.125-132
Submitted: 25 May 2022 Accepted: 14 July 2022
Published: 08 September 2022
Ischemic heart disease poses a great threat to human life with its high morbidity and mortality. Timely reperfusion is considered as the most effective intervention for clinical treatment of myocardial ischemia. Reperfusion can commonly lead to cell death and myocardial injury. There has already been evidence that dexmedetomidine (DEX) can protect the injury of myocardial ischemia reperfusion (MI/R). The aims of this research are to explain DEX’s functions in protecting MI/R injury as well as probing into its inner mechanisms. H9c2 cells was adopted to generate the injury of MI/R cell as a result of hypoxia/reoxygenation (H/R). MTT test was used to examine cell activity and flow cytometry was utilized to check cell apoptosis rate. Western blot test was adopted to appraise the protein expressions of Parkin RBR E3 ubiquitin protein ligase (PRKN or Parkin), PTEN-induced kinase-1 (PINK1) and markers associate with autophagy (Light Chain 3-II/I (LC3-II/I)). Immunofluorescence was applied to estimate the LC3 level. Next, the function of DEX in protecting the injury of H/R induced cell by PINK1/PRKN pathway was confirmed. DEX treatment significantly promoted viability, improved apoptotic rate and increased autophagy in H9c2 cells processed by H/R. Moreover, the protein expressions of PINK1 and PRKN were boosted by DEX, suggesting that DEX induced autophagy through the activation of PINK1/PRKN signaling pathway. In later tests, PINK1 teardown weakened DEX’s effect the injury of myocardial cell induced by H/R. DEX improves MI/R injury by inducing autophagy through activating PINK1/PRKN pathway.
Myocardial ischemia-reperfusion; Dexmedetomidine; Autophagy; Apoptosis; PINK1
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