Oxytocin (OT) has shown a cardioprotective effect on myocardial ischemia/reperfusion injury (MIRI). This study aimed to investigate whether the cardioprotective effect of OT is associated with the inhibition of mast cell degranulation and inflammation.

The left anterior descending coronary artery of rats was ligated for 30 min and reperfused for 120 min to establish an ischemia and reperfusion (I/R) injury model. A preliminary experiment was conducted to evaluate the optimal dose of OT (0.01, 0.1, 1 μg/kg via intraperitoneal). The mast cell secretagogue compound 48/80 (C48/80) was used to promote the degranulation of mast cells with or without I/R injury, while rats were pretreated with OT to determine whether this compound suppresses mast cell degranulation. The expression of the inflammatory factors HMGB1 and NF-κB p65 was evaluated. A cell experiment was performed for verification.

C48/80 (0.5 mg/kg, intravenous) increased mast cell degranulation and tryptase release compared with I/R-treated alone (27.12 ± 3.52 % vs. 16.57 ± 2.23 %; 8.34 ± 1.66 ng/mL vs. 3.63 ± 0.63 ng/mL), but these effects could be decreased by OT (0.1 μg/kg, intraperitoneal) preconditioning (19.29 ± 0.74 %; 5.37 ± 0.73 ng/mL). Besides that, hemodynamic disorders, arrhythmias, cardiac edema, infarct size, histopathological damage, and the levels of cTnI, HMGB1 and NF-κB p65 were significantly increased in I/R-treated group compared with corresponding observations in the control group, and C48/80 exacerbated these injuries, but pretreatment with OT could ameliorate these effects. Furthermore, C48/80 (10 μg/mL) inhibited the viability and promoted the apoptosis of H9C2(2-1) and RBL-2H3 cells, and increased the release of cTnI and tryptase, all of which were reversed by prophylactic OT (0.01 ng/mL) treatment.

We concluded that OT pretreatment inhibits the degranulation of cardiac mast cells induced by I/R injury and downregulates the expression of the inflammatory factors HMGB1 and NF-κB p65.