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Background:The sigma receptors are a relatively novel receptor group with respect to knowledge of their effect on health.Although the sigma-1 receptor agonist PRE-084 exhibits a cardioprotective effect in some studies,the benefits in cases of myocardial ischemia/reperfusion (I/R)are not clear.The aim of this study was to explore the mechanism of action and assess the effect of PRE-084 on myocardial I/R injury in rats.Methods:In this study,rats were assigned randomly to three groups with computer (n =14 for each group):a sham group,an I/R group,and a PRE-084 group.In the PRE-084 group,rats were administered PRE-084 l h before operation.In the myocardial I/R model,the left anterior descending branch of rats was ligated and opened half an hour later.Cardiac function was assessed,and the apoptosis index was evaluated.The mechanisms of the cardioprotective effects of PRE-084 were explored.Results:PRE-084 pretreatment preserved cardiac function and reduced myocardial apoptosis (F =86.0,P ＜ 0.01) with West blotting analysis,showing significantly reduced expression of Bax (F =75.7,P ＜ 0.0 l) and cleaved-caspase 3 (F =44.7,P ＜ 0.01),along with increased expression of the Bcl-2 protein (P ＜ 0.01) and phosphorylated protein kinase B (p-Akt) (P ＜ 0.01) and phosphorylated-endothelial nitric oxide synthase (p-eNOS;P ＜ 0.01).Conclusion:PRE-084 preserved cardiac function and reduced myocardial apoptosis through the activation of Akt and eNOS.