Reproduction of inflammatory bowel diseases in experiment

Abstract

The incidence of inflammatory bowel diseases, which has recently increased, encourages sci-entists to search for the most representative and easily reproducible animal models for studying the links of pathogenesis and possible ways of treating of this pathology. This review presents analysis of the genetically-conditioned and chemically-induced models of inflammatory bowel diseases. There are discussed the most common genetically conditioned models based on defects of the immune system links, loss of components of the intestinal epithelium, or spontaneous lesions of the intestinal tube wall. It is also described the techniques of the most appropriate chemically-induced models, as well as the main pathogenetic links in the development of colitis when using chemical agents. In particular, modeling of Crohn's disease with trinitrobenzenesulfonic acid (TBSA), and ulcerative colitis – with dextran sodium sulfate (DSS), as well as other models having common pathogenetic mechanisms of inflammation in the small and large intestine, e.g. models in which acetic acid, peptidoglycan, λ-carrageenan and indomethacin are used as acting chemical agents. Taking into account the correspondence of the reproduction of pathogenetic signs of inflammatory bowel disease in animals to such in people, the complexity of reproduction and the cost of the necessary components, among the discussed techniques, the undeniable advantages belong to the DSS model of ulcerative colitis and TBSA model of the reproduction of Crohn’s disease, and also the indomethacin model of inflammatory processes of the small intestine. colon, disposition of crypts with the appearance of a wide gate between the crypt base and the muscular layer, and the occurrence of lymphocytosis. TBSA also causes significant changes in the morphological characteristics, mechanical properties and pharmacological response of the circular muscular layer of the distal intestinal regions. TBSA causes a local increase in the synthesis of proinflammatory mediators, which is associated with a neutrophil response, resulting in profound destructive changes in the distal bowel. Finally, indomethacin, which is a strong non-steroidal anti-inflammatory drug with nonspecific action, causes more damage to the distal jejunum and proximal ileum. These models allow reproducing the corresponding basic pathogenetic changes in inflammatory bowel disease, which makes it possible to study the systemic and intersystemic cause-effect relationships of pathobiochemical, histological and pathophysiological levels at different stages of the development of the disease and upon pharmacological correction. Our interest in com-parative analysis of the existing pathological models, selection of the corresponding adequate modelling schemes for use in our conditions is due to further in-depth study of the pathogenesis of inflammatory bowel disease, as well as further research of pharmacological approaches for correction of these pathological conditions.