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 1 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 Western blotting analysis, showing significantly reduced expression of Bax (F = 75.7, P < 0.01) 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.
Sigma-1受体激动剂PRE-084降低大鼠心肌缺血再灌注损伤摘要背景：Sigma受体是近年来新发现的受体，有研究表明sigma受体激动剂具有心肌保护作用，但其对心肌缺血再灌注损伤的影响目前还不清楚。本研究的目的为研究sigma受体激动剂对大鼠心肌缺血再灌注的影响及探讨其机理。 方法：42只大鼠随机分为三组：假手术组、缺血再灌注组和PRE-084组。PRE-084组术前1小时给予PRE-084，再灌注组结扎前降支半小时后松开。检测各组心功能和心肌凋亡指数，并研究其可能的机制。 结果：PRE-084预处理组心功能显著改善，凋亡指数降低， P-Akt,p-eNOS, Bcl2表达明显增强，Bax（P<0.01）和cleaved-caspase 3（P<0.01）表达明显下降。 结论：PRE-084降低大鼠心肌缺血再灌注损伤，其机理可能与激活Akt / eNOS信号通路有关。.
Keywords: Myocardial Ischemia/Reperfusion; PRE-084; Sigma-1 Receptor.