[Butorphanol alleviates ischemic arrhythmia in SD rats by up-regulating connexin 43 (Cx43) pathway through miR-1-3p]

Objective To investigate the role of butorphanol in alleviating ischemic arrhythmias and its regulatory effects on the microRNA-1-3p/connexin 43 (miR-1-3p/Cx43) pathway. Methods SD rats were divided into the following groups: control group (the treatment was the same as that of modeling, but no coronary artery ligation was performed), butorphanol group (rats were injected 50 μg/kg butorphanol into the femoral vein after the needle has penetrated the myocardial surface), inhibitor group (5 days before the experiment, 80 mg/kg miR-1-3p inhibitor was administered via the tail vein, and the other treatment were the same as the control group); model group (ligation method was used to prepare rat ischemic arrhythmia models), butorphanol pretreatment group (50 μg/kg butorphanol was given at 5 minutes before ischemic treatment, and the other treatment were the same as the model group), inhibitor pretreatment group (5 days before the experiment, 80 mg/kg miR-1-3p inhibitor was administered via the tail vein, and the other treatment were the same as the model group). According to the electrocardiogram results, the ventricular arrhythmia score in each group was evaluated. Targetscan database was used to predict the upstream miRNAs of Cx43. Real-time quantitative PCR (qRT-PCR) was used to detect the expression of miR-1-3p and Cx43 mRNA. Western blotting was performed to detect the expression of Cx43 in myocardial tissue. The binding of miR-1-3p and Cx43 mRNA was verified by double luciferase report experiment. Results Butorphanol significantly reduced the frequency of ventricular premature beat, ventricular arrhythmia score, duration of ventricular fibrillation and duration of ventricular tachycardia in ischemic arrhythmia rats, and significantly increased the expression of Cx43 protein in myocardial tissue. Subsequently, two binding sites of miR-1-3p were found in the 3' untranslated region of Cx43 mRNA. Additionally, butorphanol significantly reduced the level of miR-1-3p in myocardium. Inhibition of miR-1-3p significantly decreased the total score of ventricular arrhythmia in the rats with ischemic arrhythmia, and significantly increased the expression of Cx43 mRNA and protein. Conclusion Butorphanol can improve ischemic arrhythmia by up-regulating the expression of Cx43 mediated by miR-1-3p.