Intestinal
ischemia/reperfusion (I/R) injury is a serious condition in
intensive care patients, resulting in severe
inflammation and remote organ damage. The activation of the
mammalian target of rapamycin (mTOR)/p70 ribosomal
S6 kinase (
p70S6K) signaling pathway exerts protective effect against
ischemia/reperfusion injury.
Ghrelin, an orexigenic
hormone, inhibits the release of pro-inflammatory
cytokines, such as
interleukin (IL)-1β,
tumor necrosis factor-α and
IL-6. In this study, we investigated the effects of
ghrelin on gut I/R injury and the regulation of the mTOR/
p70S6K signaling pathway following gut I/R injury in mice. C57BL/6 mice underwent superior mesenteric artery occlusion for 45 min, followed by reperfusion for 4 h.
Ghrelin was administered at the onset of reperfusion. We assessed survival, organ injury variables, pro-inflammatory
cytokine expression and observed the histological changes of the small intestine and lungs. Our results revealed that the administration of
ghrelin inhibited the release of certain pro-inflammatory
cytokines, reduced neutrophil infiltration, attenuated organ injury and improved survival following gut I/R injury. The administration of D-Lys-GHRP6, a specific
ghrelin receptor antagonist, to a certain extent, counteracted the protective effects of
ghrelin in gut I/R-induced organ injury and mortality. To determine whether the beneficial effects of
ghrelin following gut I/R injury are associated with the mTOR/
p70S6K signaling pathway, the phosphorylation levels of mTOR and
p70S6K were detected by western blot analysis. Our results revealed that mTOR and
p70S6K phosphorylation increased in the tissue from the small intestine and pulmonary tissue in the animals treated with
ghrelin. These findings suggest that
ghrelin attenuates organ injury following gut I/R by promoting the activation of the mTOR/
p70S6K signaling pathway.