The protective effects of calcitonin gene-related peptide on gastric mucosa injury of gastric ischemia reperfusion in rats

Gastric mucosa is one of the most vulnerable tissues in human and animal. However, little is known about the effects of calcitonin gene-related peptide (CGRP) on gastric mucosa injuries induced by gastric ischemia reperfusion. The purpose of the present study was to investigate the protective effects and mechanism of CGRP on gastric mucosa injury after gastric ischemia reperfusion in rats. Thirty-six healthy Wistar rats were randomly divided into CGRP-treated, sham-operated, and control groups. Twelve rats were involved in each group. These groups were further divided into 24-h and 48-h subgroups. Gastric ischemia reperfusion injury (GI-RI) rat model was established by a 30-min celiac artery occlusion by an artery clamp, followed by 24 h or 48 h of reperfusion. CGRP (1 μg/ml) at the dose of 3 μg/kg was given intraperiloneally (IP) at the beginning of reperfusion for rats in CGRP-treated group. Saline as vehicle (3 ml/kg body weight), IP, was administered at the beginning of reperfusion for rats in control group. Sham-operated animals were subjected to an operation without GI-RI. Twenty-four hours or 48 h after operation, the samples were taken out and processed for calculating stomach mucous membrane damage index according to Guth method, detecting pathological changes of gastric mucosa tissue by light microscopy and observing the expression of gastrin (Gas) and somatostatin (SST) by immunohistochemical staining. The results showed the following: (i) gastric mucosa with diffuse edema, splinter hemorrhage and erosion, numerous endothelial cells necrosis, mucosa dissociation, and infiltration of inflammatory cells were observed in both control and CGRP-treated animals, especially in the earlier period (24 h) and then gradually healing. CGRP administration could reduce the damage of gastric mucosa. The injury index of gastric mucosa was lower in CGRP-treated group as compared with that in control group (P < 0.01). (ii) Gas expression in gastric antrum mucosa was lower in CGRP-treated group than that in control group (P < 0.01). SST expression in gastric antrum mucosa was higher in CGRP-treated group than that in control group (P < 0.01). It is concluded that CGRP regulated the secretion of Gas and SST and thus alleviated the damage of gastric mucosa induced by ischemia and reperfusion. CGRP might be a potential candidate for clinical therapy on modulating gastric mucosal protection and maintaining gastric mucosal integrity after ischemia and reperfusion of the stomach.