VX765, a Specific Caspase‐1 Inhibitor, Alleviates Lung Ischemia Reperfusion Injury by Suppressing Endothelial Pyroptosis and Barrier Dysfunction
Siyi Wu, Li Zhao, Mengling Ye, Chunxia Liu, Hao Liu, Xiaojing He, Yi Qin, Fangte Liang, Linghui Pan, Fei Lin
Abstract
Lung ischemia reperfusion injury (LIRI) is a complex pathophysiological process with high morbidity and mortality. An important pathophysiological characteristic of LIRI is endothelial barrier dysfunction, although the mechanism involved in this process remains unclear. VX765, a specific caspase‐1 inhibitor, has been shown to have a protective effect against several diseases including sepsis, atherosclerosis, and glial inflammatory disease. The objective of this study was to determine whether VX765 had a protective effect in LIRI. The results showed that lung ischemia/reperfusion (I/R) and oxygen/glucose deprivation and reoxygenation (OGD/R) induced endothelial pyroptosis and barrier dysfunction characterized by an inflammatory response. Treatment with VX765 successfully alleviated I/R‐ and OGD/R‐induced endothelial pyroptosis and barrier dysfunction by inhibiting caspase‐1 in vivo and in vitro . In conclusion, these findings showed that VX765 provided effective protection against lung I/R‐induced endothelial pyroptosis and barrier dysfunction.