[Overexpression of PPENK reduces myocardial ischemia reperfusion injury by promoting mitophagy in rats].

Objective To investigate the effect of preproenkephalin-minimalistic immunologically defined gene expression-nuclear localization signal (PPENK-MIDGE-NLS) vector postconditioning on mitophagy during myocardial ischemia reperfusion in rats. Methods Forty male SD rats were randomly divided into 4 groups: sham operation group, ischemia reperfusion group, PPENK-MIDGE-NLS group and Control-MIDGE-NLS group. Myocardial ischemia reperfusion injury model was induced by ligating left anterior descending branch of coronary artery (LAD). Sham operation group was treated identically with the ischemia reperfusion group except that LAD was not tied and occluded. Ischemia reperfusion group, PPENK-MIDGE-NLS group, and Control-MIDGE-NLS group were treated with ligation and occlusion of LAD for 30 minutes followed by 24 hour-reperfusion, with 1.5 mL saline, or 1.5 mL PPENK-MIDGE-NLS vectors (200 μg), or 1.5 mL Control-MIDGE-NLS vectors (200 μg) administered respectively right before reperfusion started. Serum cTnI was assayed by ELISA and myocardial infarct size was measured by TTC. Ultrastructural changes of mitochondria and mitophagy were observed using electron microscope, and mitochondrial damage scores were analyzed. Expressions of the mitophagy-related proteins such as PINK1, parkin, p62, TOM20 and LC3B were measured by Western blotting. Results Compared with the ischemia reperfusion group, both serum cTnI content and myocardial infarct size in the PPENK group decreased; the expression of PINK1, parkin, p62 and LC3B were all up-regulated. Mitophagy was enhanced and mitochondrial damages were alleviated, with conspicuous improvement in mitochondria ultrastructure. Conclusion PPENK-MIDGE-NLS vector postconditioning can mitigate myocardial ischemia reperfusion injury by promoting mitophagy in rats.