The degranulation of cardiac mast cells is associated with occurrence and development of myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine has a cardioprotective effect from I/R injury. The purpose of this study was to investigate whether dexmedetomidine preconditioning induced cardioprotection is related to suppression of degranulation of cardiac mast cell. Both in vivo and in vitro experimental results revealed that hemodynamic disorder, arrhythmia, infarct size, histopathological score, and mast cell degranulation were dramatically increased in I/R injury groups compared with non-I/R groups, and mastocyte secretagogue compound 48/80 aggravated these damages, but it can be improved by dexmedetomidine preconditioning. Similarly, compound 48/80 increased levels of cardiac troponin I (cTnI) and tryptase, cardiomyocytes apoptosis, and expression of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), and nuclear factor-kappa B p65 (NF-κB p65) in cardiac tissues induced by I/R injury, but it can be partially decreased by dexmedetomidine pretreatment. Compound 48/80 inhibited proliferation of H9C2(2−1) and RBL-2H3, exacerbated apoptosis of H9C2(2−1), and elevated levels of cTnI and tryptase, while both of which were abolished by dexmedetomidine pretreatment. Our data suggest that dexmedetomidine preconditioning alleviates the degranulation of mast cells and the apoptosis of cardiomyocytes caused by I/R injury, and inhibits the activation of inflammatory related factors HMGB1, TLR4, and NF-κB p65.

The role of DEX and mast cells in MIRI. I/R injury can induce activation of cardiac mast cells and accelerate the cascade release of proinflammatory factors, subsequently promote the passive secretion of HMGB1 by activating pathogen-associated molecular patterns (PAMPs), while the apoptosis and necrosis of cardiomyocytes can promote the active secretion of HMGB1. Besides, extracellular HMGB1 can activate NF-κB through TLR4, leading to apoptosis, inflammation and immune dysregulation. C48/80 stimulation can accelerate the activation of mast cells induced by I/R injury, thereby aggravating hemodynamic disorders, arrhythmia, myocardial infarction, and the production of tryptase and cTnI. However, DEX pretreatment can partially reverse these effects and improve cardiac function.