PATHOGENESIS OF GASTRIC ULCERATION DUE TO H PYLORI

这项提议的目的是调查幽门螺杆菌的作用

The goal of this proposal is to investigate the role of Helicobacter pylori in gastroduodenal ulcerogenesis using a gnotobiotic piglet model of infection. H. pylori is a newly described bacterial organism which causes gastritis in humans and is an important co-factor in peptic ulcer disease. Because of the strong association with ulcers, and because of the frequent occurrence and importance of peptic ulcer disease, this organism has engendered a great deal of interest. However, virtually nothing is known about the mechanisms by which H. pylori predisposes to ulceration. The gnotobiotic piglet model is unique because, unlike other non-primate species, piglets are susceptible to H. pylori of human origin. Furthermore, gastritis in naive piglets is lymphocytic, but gastritis in immune piglets infected with H. pylori has a neutrophilic component, similar in severity and character to the chronic active gastritis associated with H. pylori in adult humans. Thus, this model is ideally suited to studies of the pathogenesis of gastritis due to this bacterium. The first objective of this proposal will be to determine if lymphocytic or neutrophilic gastritis cause delayed healing of induced gastric erosions or ulcers in piglets. The second objective will determine if bacterial cytotoxin or cytotoxin-associated proteins contribute to such delayed healing. These studies will confirm or deny the overall hypothesis that H. pylori is a crucial co-factor in human gastric ulcerogenesis. The third objective will investigate bacterial colonization factors. It is designed to determine if H. pylori flagellar genes flaA or flaB or both promote colonization by H. pylori. Finally, factors which promote differential colonization by strains of H. pylori will be investigated.