Bufalin Ameliorates Myocardial Ischemia/Reperfusion Injury by Suppressing Macrophage Pyroptosis via P62 Pathway
Chang Li, Zhen Ma, Xiang Wei, Ying Wang, Jian Wu, Xuan Li, Xiaolei Sun, Zhiwen Ding, Cheng Yang, Yunzeng Zou
Abstract
Bufalin, which is isolated from toad venom, exerts positive effects on hearts under pathological circumstance. We aimed to investigate the effects and mechanisms of bufalin on myocardial I/R injury. In vivo, bufalin ameliorated myocardial I/R injury, which characteristics with better ejection function, decreased infarct size and less apoptosis. The levels of pyroptotic proteins were increased in I/R-treated macrophages and inflammatory cytokines expressed more in I/R-induced mouse, which could be attenuated by bufalin. Bufalin also reduced H/R-treated macrophage pyroptosis in vitro. Autophagic flux blockage and ROS accumulation were reduced by bufalin in impaired macrophages. Overexpression of p62 abrogated the anti-proptosis and anti-oxidative effects of bufalin. The levels of apoptosis related proteins were changed and TUNEL-positive ratio was raised in cardiomyocytes that received conditioned medium treatment with H/R-treated macrophages, while bufalin pretreatment could reduce apoptosis. These findings indicate that bufalin may attenuate myocardial I/R injury by suppressing macrophage pyroptosis via P62 pathway.