The Protective Effect of Capsaicin Receptor-Mediated Genistein Postconditioning on Gastric Ischemia–Reperfusion Injury in Rats
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No published study has addressed the effect of genistein postconditioning on gastric ischemia–reperfusion (GI–R) injury in rats.
To examine whether capsaicin receptor-mediated genistein postconditioning protects against gastric ischemia–reperfusion injury via the PI3K/Akt signal pathway.
Methods and Results
Chloraldurat-anesthetized rats underwent occlusion of the celiac artery for 30 min, followed by 60 min of reperfusion. Based on this animal model of gastric ischemia–reperfusion injury, genistein at doses of 100, 500 or 1,000 μg/kg was administered via peripheral vein 5 min before reperfusion. The dose of 500 μg/kg was optimal for postconditioning, at which the severity of I–R-induced gastric injury significantly decreased. Immunohistochemistry also showed that gastric mucosal cell apoptosis decreased. Capsazepine (CPZ), a specific antagonist for the capsaicin receptor, was administered (1,000 μg/kg, i.v.) just before ischemia. Capsaicin (50 mg/kg, s.c.) once a day for 4 days reversed the protective effects of genistein. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting showed increased calcitonin gene-related peptide (CGRP) expression in genistein group but not in capsazepine or capsaicin group. CGRP inhibitor CGRP8-37 also prevented the effects of genistein in decreasing gastric mucosal injury index. In addition, PI3K inhibitor LY294002 (1.5 mg/kg) reversed the protective effect of genistein. Compared with genistein group, Western blots also demonstrated decreased Akt phosphorylation in LY294002 group.
Our data suggest that capsaicin receptors mediated the protective effects of genistein postconditioning. CGRP secreted by activated capsaicin-sensitive neurons played an important role in the protective effects of genistein. PI3K/Akt pathway was also involved in the protective effects of genistein.
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- The Protective Effect of Capsaicin Receptor-Mediated Genistein Postconditioning on Gastric Ischemia–Reperfusion Injury in Rats
Digestive Diseases and Sciences
Volume 55, Issue 11 , pp 3070-3077
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- Gastric ischemia–reperfusion
- Genistein postconditioning
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- Author Affiliations
- 1. Department of Physiology, Xuzhou Medical College, Xuzhou, China
- 2. Department of Neurobiology, Xuzhou Medical College, Xuzhou, China
- 3. The Affiliated Hospital of Xuzhou Medical College, Shuyang People Hospital, Suqian, China