Mouse model of Helicobacter pylori infection: studies of gastric function and ulcer healing

Background: Helicobacter pylori infection in humans is a major risk factor for peptic ulcer, but studies on the relation between H. pylori infection a nd gastric pathology are limited due to a deficiency of convenient animal m odels resembling this infection in humans. Methods: We studied the effects of inoculation of conventional BALB/c mice with CagA and VacA positive (type I) H. pylori or CagA and VacA negative H. pylori (type II) strains on gastric secretion and healing of chronic aceti c acid-induced ulcers in mouse stomachs. The ulcer area, gastric brood flow , plasma interleukin (IL)-1 beta and IL-12, as well as plasma gastrin and g astric luminal somatostatin were determined. Gastric mucosal biopsy samples were also taken for assessment of the presence of viable H. pylori using a rapid urease test, H. pylori-culture and the RT-PCR analysis of the signal for H. pylori CagA. Results: Gastric acid and pepsin secretion was reduced by over 50% immediat ely after H. pylori inoculation and accompanied by a significant increment in plasma gastrin and fan in gastric luminal somatostatin content observed over all test days, particularly in mice infected with type I H. pylori. Th e area of ulcers in vehicle-treated controls decreased significantly starti ng from day 2 after ulcer induction and then continued to decline for a fur ther 14 days to heal almost completely after 28 days. In contrast, the ulce rs were present until day 28 in all mice infected with type I or type II H. pylori strains, being significantly larger, especially with type I H. pylo ri infection. The gastric blood flow at the ulcer margin and ulcer crater i n vehicle-treated mice gradually increased with decreasing ulcer size, afte r 14 and 28 days reaching a value which was not significantly different fro m that in vehicle-administered mice. In contrast, the gastric blood now in type I H. pylori and, to a lesser ex-tent, in type II H. pylori infected mi ce was significantly lower than in vehicle controls, both at the margin and at the crater of ulcers at all tested days. Histological changes such as o edema or congestion of surface epithelium were found after 7 days whereas m ucosal inflammatory infiltration appeared after 14 days with a further incr ease after 28 days, especially in type I H. pylori and to a lesser extent i n type II H. pylori infected mice. Plasma IL-1 beta and IL-12 were signific antly elevated at all tested days of ulcer healing and their increments wer e significantly higher in type I than in type Il H. pylori infection. Conclusions: Conventional mice with gastric ulcers can be successfully infe cted by both toxigenic and nontoxigenic H, pylori strains, and this infecti on causes an immediate suppression of gastric secretion and markedly delays the healing of ulcers due to the fall in mucosal microcirculation in the u lcer region, cytokine release and an impairment in the gastrin-somatostatin link that appears to be independent of gastritis and more pronounced with infection of toxigenic than nontoxigenic strains.