Aims: Our previous studies have shown that N-n-butyl haloperidol iodide (F2) can antagonize myocardial ischemia/reperfusion (I/R) injury by blocking intracellular Ca2+ overload and suppressing Egr-1 overexpression. The present study is to investigate the relation between the reduction of Ca2+ overload and the inhibition of Egr-1 overexpression. Methods: The Sprague-Dawley rat myocardial I/R model and cultured cardiomyocyte hypoxia-reoxygenation (H/R) model were established. Administration of Egr-1 antisense oligodeoxyribonucleotide (AS-ODN) only or combining with F2, Egr-1 protein expression was examined by Western-blot analyses. Hemodynamic parameters, creatine kinase (CK) and lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA), myeloperoxidase (MPO), cardiac troponin I (cTnI), and tumor necrosis factor-α (TNF-α) were measured to assess the degree of injury and inflammation of myocardial tissues and cells. Results: Treatment with Egr-1 AS-ODN significantly reduced Egr-1 protein expression and attenuated injury and inflammation of myocardium caused by I/R or H/R evidenced by the amelioration of hemodynamics, the decrease in leakage of CK, LDH, cTnI, the increase in MDA generation, the decrease in SOD activity, the reduction of MPO activity in myocardial tissues and release of TNF-α from cultured cardiomyocytes. Treatment with F2 combined with Egr-1 AS-ODN, the inhibition of Egr-1 protein expression and inflammation (MPO activity and TNF-α level) were not enhanced, but the protection from myocardial I/R (or H/R) injury was significantly increased in hemodynamics and cytomembrane permeability relative to the using of Egr-1 AS-ODN only. Conclusion: These data suggest that the inhibition of Egr-1 overexpression cannot involve all mechanisms of cardioprotection from I/R injury.

Keywords:
Early growth response-1, Calcium channel blocking, Antisense oligodeoxyribonucleotide, Ischemia-reperfusion, Hypoxia-reoxygenation, Myocardium, N-n-butyl haloperidol iodide
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© 2009 S. Karger AG, Basel
2009
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