The Role Of Calcitonin Gene-Related Peptide (CGRP)during The Development Of Gastric Stress Ulceration In Juvenile Rats And Its Mechanism

Gastric stress ulceration is a common complication of various serious diseases in pediatrics.Its mechanism is rather complex in relation to multiple factors, such as disturbance of neuroendocrine. Calcitonin gene-related peptide(CGRP), a new brain-gut peptide found by Rosenfeld in 1983, has been reported to increase gastric mucosal blood flow (GMBF), inhibit acid secretion, restrain gastric motility and stimulate release of somatastin. In order to explore the relationship between CGRP and the development of gastric stress ulceration. We measured dynamically the content of CGRP in gastric tissue in juvenile rats with gastric stress ulceration by radioimmunoassay. Results 0.5, 1, 3h after the restraint- water immersion stress, the contents of CGRP in whole gastric wall showed a significant decrease. Furthermore, there was a marked negative correlation between the contents of CGRP and the gastric mucosa lesion index at every spot after stress. In order to explore the role of CGRP in gastric stress ulceration in juvenile rats, we observed and evaluated the effect of CGRP on ulceration by being administered before and after stress. Results: After rat-cLCGRP (10, 50, lOOp.glkg) was administered subcutaneously to the rats 30 mm before the restraint-water immersion stress procedure and rat-c~CGRP (1 OOp.glkg) was administered subcutaneously to the rats 30 mm after the restraint-water immersion stress procedure, the gastric mucosal lesions were significant alleviated. The effect of CGRP administered before stress was superior to that after stress. In order to explore the mechanism of the protective action of CGRP in gastric stress ulceration in juvenile rats, We firstly observed the effect of exogenous CGRP on the level of nitric oxide (NO) in entire gastric wall in juvenile rats by colorimestry. Results: After rat-ctCGRP (50, 1 00~.tg/kg) was administered subcutaneously to the rats 30 mm before the restraint-water immersion stress procedure, the levels of NO in entire gastric wall were significantly increased., while the same effect was not observed in rat-txCGRP (1 Oj.tg/kg) group. On the basis of that, we further observed the effect of exogenous CGRP on the expression of nitric oxide synthase(NOS) in gastric wall in juvenile rats with gastric stress ulceration by means of colorimetry and immuno-histochemistry (IHCnvision) method and analysed the effect in qualitation and quantitation. Results: After rat-cLCGRP (10, 50,lOOp.g/kg) was administered subcutaneously to the rats 30 mm before the restraint-water..immersion stress procedure, the activities of NOS were significantly.improved. The density of distribution of NOS-positive product and thenumber of myenteric NOS-positive cells in entire gastric wall in rat-aCGar (l00pg/'kg) group were significantly increased.The results indicated that CGRP was significanly related to thedevelopment of gastric stress ulceration in juvenile rats. ExogenousCM could provide a good protective action for gastric stress ulcertion...in Juvenile rats, esPecially in prevention. It was confirmed that theprotective effect of CGRP on gastric stress ulceration in juvenile ratsmight be induced by rising the level of NO in gastric tissue, the result of'high exPression of NOS. The mechanism of gastric stress ulcerationfurther demonstrated in the study will provide a new idea to prevent andcure gastric stress ulceration in pediatrics.