Mouse model of gastric infection with cytotoxin-expressing strain of Helicobacter pylori in studying of pathogenesis of chronic gastric ulcer

• Published in: Journal of gastroenterology and hepatology 1998-11, Vol.13 (S1), p.S178-S184
• Main Authors: KONTUREK, PETER C, BRZOZOWSKI, TOMASZ, KONTUREK, STANISLAW J, KARCZEWSKA, ELZBIETA, PAJDO, ROBERT, GHIARA, PAOLO, HAHN, ECKHART G
• Format: Article
• Language: English
• Subjects: cytotoxin-associated gene A; gastric ulcer; gastritis; Helicobacter pylori; ulcer; vacuolating cytotoxin gene A
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/j.1440-1746.1998.tb01873.x

Helicobacter pylori is a major risk factor for peptic ulcer, but studies on the role of H. pylori infection in gastric pathology are limited due to lack of convenient models resembling H. pylori infection in humans. We studied the effects of inoculation of conventional BALB/c mice with a toxigenic (cytotoxin associated gene A (cagA)+ and vacuolating cytotoxin gene A (vacA+) H. pylori strain on the course of healing of gastric ulcers. Following inoculation of toxigenic H. pylori or vehicle, gastric ulcers were produced in mice, which were then killed either at day 0 or after 2, 4, 7, 14 or 28 days and ulcer area and gastric blood flow (GBF) were determined. Gastric secretions from mice with chronic gastric fistulae were studied before and after inoculation with toxigenic H. pylori or vehicle (saline). The area (7 mm2) of ulcers in control mice decreased gradually and disappeared almost completely after 14 or 28 days. The ulcers in H. pylori‐infected mice were present at all test days, showing a larger area than in vehicle control animals. The GBF in control mice rose gradually with decreasing ulcer size, being significantly higher at the ulcer margin than the ulcer crater. In contrast, the GBF in H. pylori‐infected mice was significantly lower at the ulcer area than that in the vehicle controls but, again, the GBF at the ulcer margin was always higher than at the ulcer crater. Gastric acid output was reduced by more than 50% immediately after H. pylori inoculation and was accompanied by a significant increase in plasma gastrin release and a fall in gastric luminal somatostatin content. These secretory changes persisted at all test days. Oedema/congestion of surface epithelium appeared after 7 days and mucosal inflammatory infiltration appeared after 14 days, to further increase after 28 days, upon the induction of ulcer. Plasma interleukin (IL)‐Iß and IL‐12 were significantly elevated above the initial values compared with controls. Conventional mice with gastric ulcers can be successfully infected with an H. pylori strain expressing cagA and vacA cytotoxin and this infection markedly delays healing of the ulcers, probably due to the fall in GBF in the ulcer area, mucosal inflammation, cytokine release and impairment of the gastrin‐somatostatin link.