Bufalin Ameliorates Myocardial Ischemia/Reperfusion Injury through
Attenuation of Macrophage Pyroptosis -Induced Cardiomyocyte Apoptosis
Macrophages are recruited to the heart and release inflammatory
cytokines that interact with cardiomyocytes during myocardial ischemia
reperfusion (I/R) injury. Bufalin, which was isolated from toad venom,
exerts positive effects on hearts under pathological circumstances.
However, the nature of the effects of bufalin on macrophages during
myocardial I/R injury are still unknown. In cardiomyocytes that were
cocultured with H/R-treated macrophages, ROS levels increased, and
apoptosis of cardiomyocytes was triggered. H/R-treated macrophages were
treated with bufalin, which inhibited the process of pyroptosis. Bufalin
treatment also inhibited the release of IL-1β from H/R-treated
macrophages. The apoptosis was attenuated in cardiomyocytes that were
cocultured with H/R-exposed and bufalin-treated macrophages.
Concomitantly, downregulation of LC3-II and accumulation of P62 were
observed in H/R-treated macrophages. Bufalin was found to reverse the
changes in the LC3-II and P62 levels in H/R-treated macrophages, but
overexpression of p62 inhibited the anti-pyroptotic effects of bufalin.
In vivo, Bufalin was shown to reverse the changes in the levels of the
autophagic proteins LC3-II and p62 and the pyroptotic proteins in
macrophages isolated from mice subjected to I/R. Mice that were
subjected to I/R and treated with bufalin had significantly better heart
function and a decreased infarct size; these effects occurred via the
attenuation of the changes in the level of apoptosis of cardiomyocytes.