Dezocine Suppresses Myocardial Cell Apoptosis in Rats with Myocardial Ischemia-Reperfusion Injury via TLR4/NF-κB Signaling Pathway

Abstract

Background: Myocardial ischemia-reperfusion (MI/R) injury is a leading cause of myocardial damage, characterized by apoptosis and impaired cardiac function. Dezocine, a mixed opioid receptor agonist/antagonist, has shown potential in mitigating MI/R injury, but its underlying mechanisms remain unclear.Objectives: This study aimed to evaluate the effects of dezocine on myocardial cell apoptosis in rats with MI/R injury, focusing on the TLR4/NF-κB signaling pathway.Materials and Methods: Thirty-six Sprague-Dawley rats were randomly divided into three groups: sham, model, and dezocine (n = 12 each). The sham group underwent thoracotomy without MI/R injury. The model group received normal saline prior to MI/R injury induction, while the dezocine group was administered dezocine. Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65 expression were analyzed using immunohistochemistry. Western blotting quantified Bax and Caspase-3 protein levels while quantitative polymerase chain reaction assessed their mRNA expression. Cell apoptosis was evaluated via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.Results: TLR4 and NF-κB p65 expression were significantly elevated in the model and dezocine groups compared to the sham group but notably lower in the dezocine group versus the model group. Bax and Caspase-3 protein and mRNA levels followed a similar trend. TUNEL assay results demonstrated higher apoptosis rates in the model and dezocine groups compared to the sham group, with the dezocine group showing a marked reduction in apoptosis compared to the model group (p < 0.05).Conclusion: Dezocine suppresses the TLR4/NF-κB pathway, reducing myocardial apoptosis in MI/R injury, suggesting its potential as a therapeutic agent in mitigating cardiac damage.

Keywords: Apoptosis; dezocine; ischemia-reperfusion injury; TLR4/NF-κB