The protective effects of calcitonin gene-related peptide on gastric mucosa injury after cerebral ischemia reperfusion in rats.
High is the incidence of gastrointestinal dysfunction induced by cerebrovascular disease. However, little is known about the effects of CGRP on gastrointestinal injuries induced by cerebrovascular disease. The purpose of the present study was to investigate the protective effects of calcitonin gene-related peptide (CGRP) on gastric mucosa injury after focal cerebral ischemia reperfusion in rats. Thirty healthy adult male Wistar rats were selected for this experiment and were randomly divided into CGRP-treated, sham-operated, and control groups, respectively. Ten rats were involved in each group. Focal cerebral ischemia reperfusion rat model was established by a 2-hour left middle cerebral artery occlusion (MCAO) using an intraluminal filament, followed by 46h of reperfusion. CGRP (1 microg/ml) at the dose of 3 microg/kg was injected intraperitoneally (i.p.) at the beginning of reperfusion for rats in CGRP-treated group. Saline as vehicle (3 ml/kg body weight), i.p., was administered at the beginning of reperfusion for rats in control group. Sham-operated animals were subjected to an operation without MCAO. Forty-eight hours 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, determining mast cell distribution by toluidine blue staining, and observing the expression of gastrin (Gas), somatostatin (SST), aquaporin-4 (AQP4), and basic fibroblast growth factor (bFGF) by immunohistochemical staining. The results showed that: (1) Gastric mucosa with diffuse edema, splinter hemorrhage and erosion, numerous endothelial cells necrosis, mucosa dissociation, infiltration of inflammatory cells were observed in both control and CGRP-treated animals. 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<0.05). (2) 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). AQP4 expression in gastric mucosa was lower in CGRP-treated group than that in control group (P<0.05). bFGF expression in gastric mucosa was higher in CGRP-treated group than that in control group (P<0.01). (3) The mast cell degranulation ratio in control group in gastric mucosa was significantly higher than that in CGRP-treated group (P<0.01). It is concluded that CGRP can regulate the secretion of Gas, SST, AQP(4), and bFGF, inhibit mast cell degaranulation and thus alleviate the damage of gastric mucosa induced by cerebral ischemia and reperfusion. CGRP may be one of the good candidates of potential clinical therapy drugs for regulating gastric mucosal protection and maintaining gastric mucosal integrity after cerebral ischemia and reperfusion.
Feng
Guoying
G
Department of Anatomy, Binzhou Medical College, Binzhou 256603, China.
Xu
Xiaobo
X
Wang
Qian
Q
Liu
Zhen
Z
Li
Zhenzhong
Z
Liu
Guixiang
G
D000818:Animals; D002545:Brain Ischemia / Q000150:complications*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries; D007150:Immunohistochemistry; D008297:Male; D009092:Mucous Membrane; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications*; D013272:Stomach Diseases / Q000150:complications*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D015740:Calcitonin Gene-Related Peptide