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Bufalin Ameliorates Myocardial Ischemia/Reperfusion Injury through Attenuation of Macrophage Pyroptosis -Induced Cardiomyocyte Apoptosis
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  • Xiang Wei,
  • Chang Li,
  • Ying Wang,
  • Jian Wu,
  • Xuan Li,
  • Xiaolei Sun,
  • Zhiwen Ding,
  • Cheng Yang,
  • Yun Zou
Xiang Wei
Fifth People's Hospital of Shanghai Fudan University
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Chang Li
Zhongshan Hospital Fudan University
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Ying Wang
Zhongshan Hospital Fudan University
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Jian Wu
Zhongshan Hospital Fudan University
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Xuan Li
Zhongshan Hospital Fudan University
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Xiaolei Sun
Zhongshan Hospital Fudan University
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Zhiwen Ding
Zhongshan Hospital Fudan University
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Cheng Yang
Zhongshan Hospital Fudan University
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Yun Zou
Zhongshan Hospital Fudan University

Corresponding Author:[email protected]

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Abstract

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.