Bufalin reduces myocardial infarction-induced myocardial fibrosis and improves cardiac function by inhibiting the NLRP3/IL-1β signalling pathway.

Abstract

Early inflammatory responses post myocardial infarction (MI) is associated with increased myocardial fibrosis and cardiac remodelling. The NLRP3 inflammasome, a key factor in this response, regulates the expression of interleukins (IL)-1β and IL-18. Inhibiting the inflammatory process may be beneficial for post-MI recovery. Bufalin effectively inhibits inflammation and fibrosis. The aim of this study was to evaluate the effects of bufalin and MCC950, an NLRP3 inflammasome inhibitor, as potential treatment agents for MI using an experimental mouse model. Male C57BL/6 mice were subjected to left coronary artery ligation to induce MI and subsequently treated with bufalin (0.5 mg/kg), MCC950 (10 mg/kg) or saline thrice a week for 2 weeks. After 4 weeks, cardiac function and myocardial fibrosis were evaluated. Myocardial levels of fibrotic markers and inflammatory factors were analysed using western blotting, enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction and immunofluorescence. In mice with MI, cardiac ultrasonography showed decreased cardiac function and myocardial fibrosis. Bufalin treatment restored left ventricular ejection fraction and fractional shortening and decreased the myocardial infarct size. Moreover, both bufalin and MCC950 preserved cardiac function and relieved myocardial fibrosis, with no significant difference. Hence, the present study findings suggest that bufalin can alleviate fibrosis and improve cardiac function in a mouse model by suppressing NLRP3/IL-1β signalling post-MI.