Degenerative changes in the mucoid epithelium of the stomach under the influence of stimulation of the hypothalamic hunger center

Abstract. The high prevalence of gastric ulcer and duodenal ulcer (GU) that persists to this day, and in some countries is growing, is due to the lack of detailed and systematic knowledge of the multi-link pathogenetic process of development of this pathology. The peptides that have recently been discovered to have a powerful regenerative effect, produced in the stomach, intestine and brain, are the ghrelin system, which has a local and systemic effect. At the same time, a model of GU development has not been developed that could involve both classical and ghrelin-mediated mechanisms, the effects of which have been described using morphological methods.

The aim of the study was to establish reactive changes in the gastric mucosa and to suggest their most probable causes in the model of stimulation of the hypothalamic hunger center.

Materials and methods. Paraffin sections of the mucosa of the cardiac part of the stomach were examined in three groups of sexually mature male rats (n = 18). In the rats of the experimental group, the hunger center associated with the lateral hypothalamus was stimulated with electric current for 15 minutes per day every day for a week (n = 6); electrodes were inserted into the hypothalamus of sham-operated rats (n = 6), to which no current was applied, rats of the second control were intact (n = 6). On the day of the end of the experiment, all rats were decapitated and, after removing the stomachs, histological sections of the mucosa in its cardiac part were examined. The structure of the mucous membrane was studied using light microscopy, morphometry and immunohistochemistry (to detect secretory granules of ghrelin using monoclonal antibodies). In an area of 0.015 mm2 of its free surface, the number of viable and dead mucous cells was counted, the area of the cytoplasm of viable superficial and pit mucocytes was calculated. In the deep part of the mucous membrane, the number of ghrelin-producing endocrine cells was counted and their area was determined. Morphometry was performed using the Imagescope program (Electronic Analysis, Russia). The median, upper and lower quartiles were determined using the GraphPad PRISM 6.0 program (USA).

Results. Systematic stimulation of the lateral hypothalamus structures for a week induces pronounced degenerative changes, death and inhibition of proliferation of viable mucous epithelial cells lining the gastric mucosa, a decrease in the size and number of ghrelin-producing gastrocytes.

Conclusion. The identified degenerative process of the mucoid epithelium of the gastric mucosa may be ghrelin-dependent, since it is combined with the phenomena of degeneration of ghrelin-producing gastrocytes, the systemic product of which has a pronounced regenerative effect affecting target cells in various ways. The obtained results indirectly confirm and develop the concept of a multi-link neurogenic-endocrine mechanism for the formation of erosions and gastric ulcers, and also aim to search for pharmacological methods for its treatment using our new model of targeted stimulation of the hypothalamic hunger center.