Journal
DIGESTION
Volume 92, Issue 4, Pages 211-219Publisher
KARGER
DOI: 10.1159/000439300
Keywords
Intestinal ischemia-reperfusion injury; Rapamycin; Mammalian target of rapamycin; Remote lung injury
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Funding
- Japan Society for the Promotion of Science [25460958, 25460959]
- Japan Science and Technology Agency
- Grants-in-Aid for Scientific Research [25460959, 25460958] Funding Source: KAKEN
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Background/Aims: Acute-phase intestinal ischemia-reperfusion (I-R) injury can result in multiple organ failure, which may sometimes be fatal. However, no reliable treatment for this clinical state is available. Rapamycin has been reported to protect heart, brain and kidney against I-R injury. The aim of this study was to examine whether rapamycin could protect mice against I-R-induced intestinal and remote organ injury. Methods: Ischemia was induced in the intestine of C57BL/6 mice by occluding the superior mesenteric artery for 1 h. Mice received rapamycin at a dose of 5 mg/kg or vehicle by the intraperitoneal injection 1 h before ischemia. The survival rate, inflammatory responses in the intestine and the lung, bacteria cultured from lung tissue and the phagocytic capacity of alveolar macrophages were examined. Results: Treatment with rapamycin improved survival rate after intestinal I-R. Histological and biochemical parameters of I-R-induced intestinal injury/inflammation were similar in both rapamycin-treated and untreated mice. However, signs of lung injury/inflammation were significantly attenuated in rapamycin-treated mice compared to control mice. The reduction of lung bacteria and the increase in phagocytic activity were accompanied in mice treated with rapamycin. Conclusion: Rapamycin improved mortality following intestinal I-R via the inhibition of remote lung inflammation in mice. (C) 2015 S. Karger AG, Basel
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