Ischemia-reperfusion injury (IRI) of the liver is a severe complication that can follow hemorrhagic shock and liver surgery. Regulatory T cells (Treg) show the potential of improving outcomes of IRI. Everolimus is an mTOR inhibitor used in liver transplantation and the treatment of tumor patients through PI3K/AKT/mTOR pathway. The present study was designed to investigate the efficacy and mechanism of everolimus on Treg for the treatment of IRI. Hepatocytes were exposed to H2O2 and hypoxic conditions to investigate the effects of everolimus on reactive oxygen species ROS-induced and H/R-induced injury in vitro. The effects of everolimus on liver IRI were investigated in a warm ischemia liver model in vivo. Our results indicate that everolimus markedly protected liver IRI in vivo and vitro. Furthermore, everolimus increased the levels of phospho- (p-)AKT, p-mTOR but not p-GSK following IRI. Taken together, our data showed that everolimus protected against IRI via regulation of caspase-3/Treg and the PI3K/AKT/mTOR signalling pathway, which provides new insight into the treatment of liver IRI.
Keywords: Everolimus; Ischemia-reperfusion injury; Treg; caspase-3.
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