Abstract | BACKGROUND: 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.
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Authors | Chuiliang Liu, Zhiwen Shen, Yanhui Liu, Jun Peng, Liping Miao, Weian Zeng, Yujuan Li |
Journal | Surgery
(Surgery)
Vol. 157
Issue 5
Pg. 924-33
(May 2015)
ISSN: 1532-7361 [Electronic] United States |
PMID | 25666336
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- Anesthetics, Inhalation
- Methyl Ethers
- Sevoflurane
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
|
Topics |
- Anesthetics, Inhalation
(administration & dosage)
- Animals
- Apoptosis
(drug effects)
- Blood Gas Analysis
- Drug Evaluation, Preclinical
- Hemodynamics
(drug effects)
- Intestinal Diseases
(prevention & control)
- Intestinal Mucosa
(drug effects)
- Intestines
(blood supply)
- Ischemic Preconditioning
- Male
- Methyl Ethers
(administration & dosage)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Random Allocation
- Rats, Sprague-Dawley
- Reperfusion Injury
(prevention & control)
- Sevoflurane
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