The effects of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 during myocardial ischemia/reperfusion in a model of rats with depression

Abstract

BackgroundMajor depressive disorder (MDD) is an independent risk factor for coronary heart disease (CHD), and influences the occurrence and prognosis of cardiovascular events. Although there is evidence that antidepressants may be cardioprotective after acute myocardial infarction (AMI) comorbid with MDD, the operative pathophysiological mechanisms remain unclear. Our aim was therefore to explore the molecular mechanisms of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 in a rat model of depression during myocardial ischemia/reperfusion (I/R).MethodsRats were divided randomly into 3 groups (n = 8): D group (depression), DI/R group (depression with myocardial I/R) and escitalopram + DI/R group. The rats in all three groups underwent the same chronic mild stress and separation for 21 days, at the same time, in the escitalopram + DI/R group, rats were administered escitalopram by gavage (10 mg/kg/day). Ligation of the rat’s left anterior descending branch was done in the myocardial I/R model. Following which behavioral tests were done. The size of the myocardial infarction was detected using 1.5% TTC dye. The Tunel method was used to detect apoptotic myocardial cells, and both the Rt-PCR method and immunohistochemical techniques were used to detect the expression of Bcl–2 and Bax.ResultsCompared with the D and DI/R groups, rats in Escitalopram + DI/R group showed significantly increased movements and sucrose consumption (P < .01). Compared with the DI/R group, the myocardial infarct size in the escitalopram + DI/R group was significantly decreased (P < .01). Compared with the D group, there were significantly increased apoptotic myocardial cells in the DI/R and escitalopram + DI/R groups (P < .01); however compared with the DI/R group, apoptotic myocardial cell numbers in the escitalopram + DI/R group were significantly decreased (P < .01). Compared with the DI/R group, there was a down-regulated Bax:Bcl-2 ratio in the escitalopram + DI/R group (P < .01).ConclusionsThese results suggest that in patients with AMI comorbid with MDD, there is an increase in pro-apoptotic pathways that is reversed by escitalopram. This suggests that clinically escitalopram may have a direct cardioprotective after acute myocardial infarction.

Icariin Exerts Protective Effect Against Myocardial Ischemia/Reperfusion Injury in Rats

“…Bcl-2 and Bax are two apoptosis-related molecules involved in I/R injury [10]. In this study, we also examined the expression levels of Bcl-2 and Bax.…”

The effect of hydroxy safflower yellow A on coronary heart disease through Bcl‑2/Bax and PPAR‑γ

“…The occurrence and progression of cell apoptosis is regulated by various genes, of which Bcl-2 serves a fundamental role via the mitochondrial pathway (19). Bcl-2 is an anti-apoptosis gene while Bax is the pro apoptotic gene (20). Additionally, HSYA significantly reduced the Bax/Bcl-2 ratio in swine with coronary heart disease.…”

“…The mitochondrial pathway is one of the most important apoptosis signal transduction pathways (20). The occurrence and progression of cell apoptosis is regulated by various genes, of which Bcl-2 serves a fundamental role via the mitochondrial pathway (19).…”

Liraglutide-induced reduction of myocardial ischemiareperfusion injury in rats via ERK1/2 signaling pathway

“…In the mitochondrial membrane, Bcl-2 and Bax are involved in the control of mitochondrial permeability to cytochrome c. It is known that the mitochondrial permeability of cytochrome c is reduced when Bcl-2 molecules form homodimers, but is increased when Bax forms heterodimers with Bcl-2 [13,14]. Thus the Bcl-2/Bax ratio is a critical factor that regulates mitochondrial apoptosis: decreased the expression of Bcl-2 and increased the expression of Bax result in increases in mitochondrial membrane permeability to cytochrome c, thereby initiating apoptosis through caspase-8/caspase-3 [15,16].…”