Effects of N-n-butyl Haloperidol Iodide on Myocardial Ischemia/Reperfusion Injury and Egr-1 Expression in Rat

摘要

We have previously shown that N-n-butyl haloperidol iodide (F_2)derived from haloperidol reduces ischemia/reperfusion-induced myocardial injury by blocking intracellular Ca~(2+)overload.This study tested the hypothesis that cardio-protection with F_2 is associated with an attenuation in the expression of early growth response gene 1 (Egr-1).In an in vivo rat model of 60 min coronary occlusion followed by 180 min of reperfusion,treatment with F_2 significantly reduced myocardial injury evidenced by the reduction in release of plasma creatine kinase,myocardial creatine kinase isoenzyme and lactate dehydrogenase.In cultured neonatal rat cardiomyocytes of hypoxia for 3 h and reoxygenation for 1 h,F_2 treatment attenuated necrotic and apoptotic cell death,as demonstrated by electron microscopy.Concomitant with cardio-protection by F_2,the increased expression levels of Egr-1 mRNA and protein were significantly reduced in myocardial tissue and cultured cardiomyocytes as detected by reverse transcription-polymerase chain reaction,immunohistochemistry and immunocytochemistry.In conclusion,these results suggest that the protective effect of F_2 on ischemia/reperfusion-or hypoxia/reoxygenation-induced myocardial injury might be partly mediated by downregulating Egr-1 expression.