Abstract
Purpose: To investigate the effect of morphine preconditioning on myocardial ischemia reperfusion injury in heart failure rats, and the mechanism(s) of action involvedMethods: Seventy-two healthy male Sprague-Dawley rats were assigned to 4 groups: sham, model, morphine-preconditioning and SB203580 inhibitor groups, each with 18 rats. The expressions of P-p38, p-glycogen synthetase kinase-3, and p-gap junction protein 43 in rat myocardial cells were assayed by Western blotting. The mRNA expression levels of Bcl-2 and Bax, and Bcl-2/Bax were determined using real-time fluorescence quantitative PCR.Results: The expression levels of P-p38, p-glycogen synthetase kinase-3, p-gap junction protein 43, Bcl-2 mRNA and Bcl-2/Bax were significantly higher in the pretreatment group than in the model group, while Bax mRNA was significantly lower (p < 0.05). Moreover, the mRNA expression levels of P-p38, pglycogen synthetase kinase-3, p-gap junction protein, Bcl-2, and Bcl-2/Bax in inhibitor-treated rats decreased significantly, when compared to the values for pretreatment rats; furthermore, Bax mRNA was markedly upregulated (p < 0.05).Conclusion: Morphine preconditioning significantly inhibits the expressions of GSK-3β and Cx43 signaling proteins, as well as apoptosis-related gene, Bcl-2 and Bax. In addition, it inhibits the apoptosis of rat cardiomyocytes, and reduces myocardial injury, after ischemia reperfusion, via activation of the p38 MARK signaling pathway. This provides a new strategy for clinical reduction of myocardial injury after ischemia-reperfusion.
 Keywords: Morphine, Pretreatment, GSK-3β/Cx43 signaling protein, Bcl-2/Bax, Heart failure, Ischemiareperfusion injury
Highlights
Coronary artery disease is considered the main cause of morbidity and mortality globally
Myocardial infarction area in pretreatment rats was markedly decreased, relative to model rats, but it was markedly increased in inhibitor-treated rats
Myocardial cell viability was significantly higher in pretreatment rats than in model rats, but was markedly less in inhibitortreated rats than in pretreatment rats (p < 0.05)
Summary
Coronary artery disease is considered the main cause of morbidity and mortality globally. The incidence of coronary heart disease in China is gradually increasing and showing a trend towards younger people [1]. With increase in the aging population, heart failure patients are prone to perioperative. -©---2-0--2--0---T--h-e---a--u-t-h--o-r-s--.--T-h--i-s--w--o--r-k--i-s--l-i-c-e--n-s--e--d--u--n-d--e--r--th--e---C--r-e-a--t-i-v-e---C--o--m--m--o-T-n-r-so--pA--t-Jt-r-iP-b-hu--at-ior--mn---4R-.-e0-s--I,n-J-t-ue--rn-ne-a--2t-i0o--2n--0a-;l--L1--i9c-(-e-6n-)-s:--e1--1--7-3 myocardial ischemia and reperfusion injury during cardiac or non-cardiac surgery, with serious effect on the quality of life and safety of patients [2]. Studies have found that post-myocardial ischemia reperfusion increases myocardial infarction area and myocardial cell apoptosis, thereby seriously affecting cardiac function recovery and endangering the lives and safety of patients [3]. A traumatic stimulation, is the most classical and effective method for protecting the myocardium from ischemic perfusion injury [4]. Morphine is an opioid which significantly reduces myocardial suppression and the incidence of heart failure [5]
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