Ghrelin attenuates intestinal ischemia/reperfusion injury in mice by activating the mTOR signaling pathway

  • Authors:
    • Hongwei Zhang
    • Zhongyi Cui
    • Guangwei Luo
    • Jiaheng Zhang
    • Tao Ma
    • Na Hu
    • Tianpen Cui
  • View Affiliations

  • Published online on: July 19, 2013     https://doi.org/10.3892/ijmm.2013.1452
  • Pages: 851-859
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Abstract

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.
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October 2013
Volume 32 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhang H, Cui Z, Luo G, Zhang J, Ma T, Hu N and Cui T: Ghrelin attenuates intestinal ischemia/reperfusion injury in mice by activating the mTOR signaling pathway. Int J Mol Med 32: 851-859, 2013.
APA
Zhang, H., Cui, Z., Luo, G., Zhang, J., Ma, T., Hu, N., & Cui, T. (2013). Ghrelin attenuates intestinal ischemia/reperfusion injury in mice by activating the mTOR signaling pathway. International Journal of Molecular Medicine, 32, 851-859. https://doi.org/10.3892/ijmm.2013.1452
MLA
Zhang, H., Cui, Z., Luo, G., Zhang, J., Ma, T., Hu, N., Cui, T."Ghrelin attenuates intestinal ischemia/reperfusion injury in mice by activating the mTOR signaling pathway". International Journal of Molecular Medicine 32.4 (2013): 851-859.
Chicago
Zhang, H., Cui, Z., Luo, G., Zhang, J., Ma, T., Hu, N., Cui, T."Ghrelin attenuates intestinal ischemia/reperfusion injury in mice by activating the mTOR signaling pathway". International Journal of Molecular Medicine 32, no. 4 (2013): 851-859. https://doi.org/10.3892/ijmm.2013.1452