Estudo histopatológico e imuno-histoquímico da mucosa gástrica de gerbils (Meriones unguiculatus) infectados por linhagens de Helicobacter pylori com diferentes ilhas de patogenicidade

Abstract

Helicobacter pylori (H. pylori) is a bacterium that infects chronically the gastric mucosa in more than half of the world population and it is related to the development of chronic gastrits, duodenal and gastric ulcers, gastric adenocarcinoma and lymphoma cutaneous B, from the marginal zone of the lymphoid tissue associated to the mucosa (linfoma MALT). There are studies in humans demonstrating that the infection by strains of H. pylori containing more than one site of CagA phosphorylation, is related to the development of more severe gastric lesions. With the absence of experimental studies on the subject, the objective of this study was to evaluate the effects of infection with H. pylori strains containing different numbers of CagA phosphorylation sites on the gerbis Mongolian gastric mucosa, in relation to the macroscopic and microscopic changes, the number of D and G cells and the the expressiveness of and MUC5AC mucins in different periods of the infection process. 48 gerbis Mongolian 3-months-old females were divided in three experimental groups: one control group consisting of non-infected animals; animals treated with H. pylori positive lineage containing one segment EPIYA-C (CagA1Ep) and animals inoculated with H. pylori CagA lineage with three segments EPIYA-C (CagA3Ep). Each group was composed of 16 animals; 8 animals of each group were sacrificed 45 days post-infection and the 8 remaining animals were sacrificed 6 months post-infection. At 45 days post-infection there was a progressive and significant increase in the number of inflammatory cells and in the site of the typical slide of the CagA1Ep and CagA3Ep groups in relation to the control group, this increase being most significant in the CagA3Ep group. During this infection period it was observed a decrease in the number of D cells in the CagA3Ep. At 45 days it was also observed a decrease in the total site of MUCI and MUC5AC mucins in the groups CagA1Ep and CagA3Ep, in relation to the control group, this being more intense in the group CagA3Ep. 6 months post-infection all the changes mentioned at 45 days were much more intense, occurring a progressive and significant increase in the inflammatory infiltrate, as well as in the site of the typical slide in the infected groups, mainly in the CagA3Ep. In this same group there was na increase of G cells and a reduction in the number of D cells. It was observed a significant and progressive decrease in the expressiveness of MUCI and MUC5AC mucins in the group of infected animals, this being more prominent in CagA3Ep group. At 6 months of infection it was also observed atrophy, intestinal metaplasia and dysplasia this being more frequent in CagA3Ep group. The results showed that H. pylori lineages containing a greater number of phosphorylation sites are sifnificantly more pathogenic than strains with only one site of phosphorylation EPIYA-C, leading to the development of more severe chronic gastrits and frequently to the development of pre-cancerous lesions.