GASTRIC-SECRETION AND ULCER HEALING IN MOUSE STOMACH INFECTED WITH CYTOTOXIN EXPRESSING STRAIN OF HELICOBACTER-PYLORI

Helicobacter pylori (Hp) is a major risk factor of peptic ulcer but st udies on the relation between Hp infection and gastric pathology are l imited due to lack of convenient models resembling Hp infection in hum ans. We studied the effects of inoculation of conventional BALB/c mice with toxigenic type I Hp (cagA+ and vacA +) and non-toxigenic type II Hp (cagA- and vacA-) vs administration of vehicle on gastric secretio n and healing of gastric ulcers. The gastric secretion studies were pe rformed on mice with chronic gastric fistula before and after inoculat ion with toxigenic or non-toxigenic Hp strain or administration of veh icle (saline). Gastric ulcers were produced in mice inoculated with to xigenic and non-toxigenic Hp strain or vehicle and then sacrificed at day 0 and after 2, 4, 7, 14 and 28 days. Ulcer area and gastric blood flow (GBF), plasma gastrin and gastric luminal somatostatin were deter mined. Gastric mucosal biopsy specimens were also taken for the assess ment of the presence of viable Hp using rapid urease test, the Hp-cult ure and the reverse transcriptase - polymerase chain reaction (RT-PCR) analysis of the signal for Hp CagA. Gastric acid output was reduced b y over 50% immediately after Hp inoculation and this effect persisted during all time intervals tested, being significantly more pronounced in type I Hp-infected stomach. The area (7 mm(2)) of ulcers in control mice decreased gradually and then continued to decline during 14 days to disappear almost completely after 28 days. In contrast, the ulcers were present till day 28 in all mice infected with type I or type II Hp strain being significantly larger especially with type I Hp-infecti on. The GBF in control mice showed gradual rise with decreasing ulcer size being significantly higher at the ulcer margin than the ulcer cra ter and reached after 14 and 28 days the value not significantly diffe rent from that in vehicle-administered mice. In contrast, the GBF in t ype I Hp-infected mice but to a lesser extent,in type II Hp infected m ice was significantly lower than in the vehicle controls, both at the ulcer margin and the crater of ulcers at all tested days. Hp-infection was accompanied by significant increment in plasma gastrin and the fa ll in gastric somatostatin contents observed at all test days; particu larly in mice infected with type I Hp strain. Edema of surface epithel ium appeared after 7 days and weak but significant mucosal inflammator y infiltration occurred after 14 days to further increase after 28 day s, especially in type I Hp and less in type II Hp infected mice. We co nclude that conventional mice with gastric ulcers can be successfully infected by both toxigenic and non-toxigenic Hp strains and this infec tion markedly reduces gastric acid secretion and delays healing of ulc ers probably due to the fall in mucosal microcirculation in ulcer area , mucosal inflammation and impairment in gastric-somatostatin link.