Oxytocin Ameliorates Myocardial Ischemia-reperfusion Injury By Inhibiting Mast Cell Degranulation In The Rat

Objectives:To investigate whether oxytocin could ameliorate myocardial ischemia-reperfusion injury,and whether this cardioprotective effects could be carried out by inhibition of mast cell degranulation and inflammation.Methods: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.Results:C48/80(0.5mg/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(0.1μg/kg,intraperitoneal)preconditioning(19.29±0.74%;5.37±0.73ng/mL).Besides that,hemodynamic disorders,arrhythmias,cardiac edema,infarct size,histopathological damage,and the levels of cTnl、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 increased the release of cTnI and tryptase.Conclusion(s)(1)Oxytocin can ameliorate myocardial ischemia-reperfusion injury;(2)Compound48/80 can aggravate myocardial ischemia-reperfusion injury by accelerating mast cell degranulation and inflammation.(3)Oxytocin can ameliorate myocardial ischemia-reperfusion injury by inhibiting mast cell degranulation and inflammation.