Resveratrol pretreatment protects rat hearts from ischemia/reperfusion injury partly via a NALP3 inflammasome pathway

摘要

Inflammatory responses are key players in myocardial ischemia/reperfusion (I/R) injury. Our previous studies showed that resveratrol alleviated I/R injury in myocardial I/R animal models, but whether the NALP3 inflammasome pathway contributes to the mechanisms remains to be elucidated. In this study, we explored the modulation effect of resveratrol on myocardial I/R-induced inflammatory responses in rats. Myocardial I/R rat animal models were induced by occlusion of the left anterior descending coronary arteries (LADs) for 30 min, followed by 2 h of reperfusion. Resveratrol was administered in different doses (2.5, 5, and 10 mg/kg) at the same time as the onset of reperfusion. The serum concentrations of the trinitrotoluene (TnT) and MB isoenzyme creatine kinase (CK-MB) were detected using an automatic biochemical analyzer. Myocardial ultrastructure and morphology were observed with an electron microscope and a light microscope. Myocardial ischemia and infarct sizes were evaluated using Evans blue and tetrazolium chloride (TTC) staining. The NALP3, Caspase1, interleukin 1β (IL-1β) and interleukin 18 (IL-18) mRNA levels were evaluated using RT-PCR. The NALP3 and Caspase1 protein expression levels were detected by western blotting. The IL-1β and IL-18 content in peripheral blood was measured by enzyme-linked immunosorbent assay (ELISA). The myocardial structure in myocardial ischemia reperfusion injury (MI/RI) rats was extensively damaged. After preconditioning with different concentrations of resveratrol (2.5, 5 and 10 mg/kg), the pathology and morphology were significantly improved in a dose-dependent manner. Our results showed that resveratrol treatment significantly reduced the infarct volume and myocardial fibrosis, resulting in myocardial cells that lined up in a more orderly fashion and dose-dependent decreases in TnT and CK-MB levels in the serum of the I/R rats. Resveratrol also significantly modulated mRNA and protein levels by down-regulating NALP3 and Caspase1 expression and IL-1β and IL-18 activation. These results suggest that the NALP3 inflammasome is activated during the myocardial I/R injury process and that the secretion of the inflammatory cytokines IL-1β and IL-18 mediates the cascade inflammatory response. Resveratrol may play an important role in protecting the myocardium against I/R injury in rats by inhibiting the expression and activation of the NALP3 inflammatory body. Therefore, the attenuation of the inflammatory response may be involved in the cardioprotective mechanisms of resveratrol in response to myocardial I/R injury.