Elsevier

Surgery

Volume 157, Issue 5, May 2015, Pages 924-933
Surgery

Inflammation
Sevoflurane protects against intestinal ischemia–reperfusion injury partly by phosphatidylinositol 3 kinases/Akt pathway in rats

https://doi.org/10.1016/j.surg.2014.12.013Get rights and content

Background

Intestinal ischemia–reperfusion injury (IRI) is a clinical challenge with high morbidity and mortality, leading to intestine damage, systemic inflammation, and multiorgan failure. Previous research has shown that the inhaled anesthetic sevoflurane protects various organs from IRI. However, whether sevoflurane protects against intestinal IRI and which application condition is the most effective are not completely clear. Thus, we investigated the effects of sevoflurane on intestinal IRI with sevoflurane given before, during or after intestinal ischemia, and the role of phosphatidylinositol 3 kinases (PI3K)/Akt pathway in these effects.

Methods

Rat model of intestinal ischemia–reperfusion (IR) was used in this study. The superior mesenteric artery was clamped for 60 minutes followed by 120 minutes of reperfusion. Sevoflurane at 0.25, 0.5, and 1.0 minimum alveolar concentration (MAC) was inhaled for 30 minutes before, during, or after ischemic insult. LY294002, a PI3K inhibitor, was injected intraperitoneally before sevoflurane inhalation.

Results

Intestinal IR caused a significant decrease of mean arterial blood pressure, severe intestinal mucosa injury and epithelial cell apoptosis, downregulation of the levels of phospho-Akt and phospho-Bad proteins. Exposure to 0.5 or 1.0 MAC sevoflurane before or after intestinal ischemia or 0.5 MAC during intestinal ischemia significantly ameliorated IR-induced histopathologic changes and decreased Chiu's scores. Pretreatment with 0.5 MAC sevoflurane also inhibited intestinal IR-induced increase of terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling–positive cells and activation of caspase-3 and restored expression of phospho-Akt and phospho-Bad. LY294002 partly blocked the protective effects induced by 0.5 MAC sevoflurane pretreatment.

Conclusion

Our results suggest that sevoflurane inhalation at clinical related concentration before, during, or after ischemia protects against IR-induced intestinal injury. The pretreatment-induced protection was partly mediated by inhibiting intestinal mucosal epithelial apoptosis via activation of the PI3K/Akt pathway.

Section snippets

Materials and methods

All experimental procedures and protocols in this study were approved by the animal care committee at Sun Yat-sen University, Guangzhou, China, and were performed in strict accordance with National Institutes of Health Guidelines for the use of experimental animals. All efforts were made to minimize suffering of the animals.

Adult, male Sprague-Dawley rats weighing 200–220 g were obtained from Guangdong Medical Laboratory Animal Co, China (Permission number: SCXK 2008-0002). They were housed

Effects of sevoflurane preconditioning on hemodynamics and blood gases

Intestinal IR led to a significant decrease of MAP compared with sham control animals. The decrease of MAP in the reperfusion period was more severe than that in the ischemia period. Exposure to sevoflurane at both 0.5 and 1.0 MAC before ischemia (pretreatment) alleviated significantly intestinal IR-induced decrease of MAP in the reperfusion period (Fig 2), but not that in the ischemia period. Pretreatment with sevoflurane at 0.25 MAC had no effect on IR-induced decrease of MAP (Fig 2).

Discussion

The present study has demonstrated that exposure to clinically relevant concentrations of sevoflurane at 0.5 or 1.0 MAC before or after intestinal ischemia as well as sevoflurane at 0.5 MAC during intestinal ischemia reduced intestinal IRI. Rats pretreated with 0.5 MAC sevoflurane exhibited the greatest protective effects among all the treatments. In addition, PI3K/Akt signaling pathway activation may be one of the mechanisms for pretreatment with 0.5 MAC sevoflurane to reduce intestinal

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    • Cited by (0)

    C.L. and Z.S. are considered co-first authors on this article.

    Supported by grants from the National Science Foundation of China (grant number: 81371259) to Yujuan Li, and the Guangdong Natural Science Foundation (grant number: S2013010016207) to Yujuan Li.

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