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

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

Qi-Jun Gao, Bo Yang, Jing Chen, Shao-Bo Shi, Hong-Jie Yang, Xin Liu

Chin Med J (Engl). 2018 Mar 5;131(5):539-543.

PMID: 29483387

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4244479	PRE-084			Price

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