Sigma-1 Receptor Stimulation with PRE-084 Ameliorates Myocardial Ischemia-Reperfusion Injury in Rats  

作　　者：Qi-Jun Gao Bo Yang Jing Chen Shao-Bo Shi Hong-Jie Yang Xin Liu 

机构地区：[1]Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, China [2]Department of Cardiology, First Hospital of Jingmen, Jingmen, Hubei 448000, China

出　　处：《Chinese Medical Journal》2018年第5期539-543,共5页中华医学杂志（英文版）

摘　　要：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 I 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.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 I 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.

关 键 词：Myocardial Ischemia/Reperfusion PRE-084 Sigma-1 Receptor 

分 类 号：Q463[生物学—生理学] X503.2[环境科学与工程—环境工程]