| Objective To investigate the effect of acacetin(Aca) on myocardial cell pyroptosis in rats with myocardial ischemiareperfusion injury(MIRI) and its regulatory mechanism on the high mobility group B1/receptor for advanced glycation endproducts(HMGB1/RAGE) signaling pathway. Methods Rats were randomly divided into six groups: the sham-operated group(Sham group), the model group(Model group), the low-dose Aca group(Aca-L group), the medium-dose Aca group(Aca-M group), the high-dose Aca group(Aca-H group), and the high-dose Aca combined with HMGB1/RAGE activator DEX group(Aca-H+DEX group). The histopathological changes of myocardial tissue, left ventricular internal dimension at systole(LVIDs), left ventricular ejection fraction(LVEF), left ventricular internal dimension at diastole(LVIDd), serum levels of creatine kinase-MB(CK-MB) and lactate dehydrogenase(LDH), concentrations of interleukin-18(IL-18) and interleukin-1β(IL-1β), cardiomyocyte apoptosis rate, as well as the expression levels of HMGB1/RAGE signaling pathway-related proteins and pyroptosis-associated molecules in myocardial tissue were observed or detected in each group, respectively. Results Compared with the sham group, the cardiomyocytes in the model group showed swelling and disordered arrangement, accompanied by cell necrosis and inflammatory infiltration. Meanwhile, the LVEF value significantly decreased(P<0.05), whereas the LVIDd value, LVIDs value, serum levels of CK-MB, LDH, IL-1β and IL-18, cardiomyocyte apoptosis rate, as well as the expression levels of HMGB1, RAGE, NLRP3, caspase-1 and GSDMD in myocardial tissue notably increased(P<0.05). With the administration of Aca and the increase of its dosage, the histopathological damage of myocardial tissue was alleviated, the number of necrotic cells was reduced, and the degree of inflammatory infiltration was mitigated. Additionally, the cardiac function was enhanced, and the serum levels of myocardial injury markers, cardiomyocyte apoptosis rate, together with the exP pression levels of HMGB1/RAGE pathway-related proteins and pyroptosis-associated molecules in myocardial tissue decreased(<0.05). However, DEX partially reversed the inhibitory effect of Aca on cardiomyocyte pyroptosis in rats with myocardial ischemia-reperfusion injury(MIRI)(P<0.05). Conclusion Aca can inhibit cardiomyocyte pyroptosis in rats with MIRI, and its underlying mechanism may be associated with the suppression of the HMGB1/RAGE signaling pathway. |
