A study on the molecular mechanism of cardiac protection of procarboxylpeptidase in MIRI rats based on the NLRP3 signaling pathway.

Abstract

ObjectiveTo investigate the way in which prolylcarboxypeptidase (PRCP) protects against myocardial ischemia-reperfusion injury (MIRI) and the mechanisms that underlie it.MethodA surgical ligation of the coronary artery was adopted to establish a myocardial ischemia-reperfusion model in male SD rats. Thirty-six rats were randomly divided into six groups: Normal group, Sham group, MIRI model group, empty vector (MIRI + EZ.null) group, PRCP overexpression (MIRI + PRCP) group, and nicorandil (MIRI + Nic) group, with 6 rats in each group. The rats received an injection of PRCP's adeno-associated virus 9 (AAV9) through the tail vein 3 weeks prior to the modeling.ResultsCompared with the Normal and Sham groups, the expression levels of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), Caspase-1, IL-18, IL-1β, and GSDMD in the MIRI group and MIRI + EZ-null group were significantly increased (P < 0.05). Myocardial apoptosis index, myocardial infarction size, ejection fraction, and short axis shortening rate were significantly increased (P < 0.05). At the same time, PRCP and nicorandil therapy could reverse the damage effect caused by MIRI (P < 0.05).ConclusionPRCP can lessen MIRI and protect cardiac function in rats by inhibiting NLRP3/Capase-1/IL-18/IL-1β signaling pathway-mediated cell pyroptosis.