Helicobacter pylori-induced chronic active gastritis, intestinal metaplasia, and gastric ulcer in Mongolian gerbils

Abstract

The establishment of persisting Helicobacter pylori infection in laboratory animals has been difficult, but in 1996 Hirayama reported the development of a successful Mongolian gerbil model. The present study was undertaken with two aims: to better characterize the normal histological structure and histochemical properties of the gastric mucosa of the Mongolian gerbil; and to evaluate the progression of the histopathological features of H. pylori-induced gastritis in this animal model for one year after the experimental infection. Seventy-five Mongolian gerbils were used. Mongolian gerbils were sacrificed at 2, 4, 8, 12, 26, 38, and 52 weeks after H. pylori inoculation. Sections prepared from stomachs immediately fixed in Carnoy's solution were stained with hematoxylin and eosin and Alcian blue at pH 2.5/periodic acid-Schiff, a dual staining consisting of the galactose oxidase-cold thionin Schiff reaction and paradoxical Concanavalin A staining, and with immunostaining for H. pylori and BrdU. H. pylori infection induced in the Mongolian gerbil a chronic active gastritis, in which a marked mucosal infiltration of neutrophils on a background of chronic inflammation became detectable 4 weeks after inoculation and continued up to 52 weeks. Intestinal metaplasia and gastric ulcers appeared after 26 weeks in some of the animals, whereas others developed multiple hyperplastic polyps. The Mongolian gerbil represents a novel and useful model for the study of H. pylori-induced chronic active gastritis and may lend itself to the investigation of the epithelial alterations that lead to intestinal metaplasia and gastric neoplasia.

Figure 1.

Macroscopic findings of the Mongolian gerbil stomach. a: Normal control. b. 4 weeks after inoculation of H. pylori. Antral mucosa slightly expands. c: 26 weeks after inoculation of H. pylori. Ulcer is formed at the border between pyloric mucosa and fundic mucosa (arrows). d: 26 weeks after inoculation of H. pylori. Many sessile polyps are found around the border between pyloric mucosa and fundic mucosa (arrows).

Figure 2.

Histology of normal stomach of Mongolian gerbil. a: Cardiac mucosa. Cardiac glands are recognized around the border between forestomach and gland stomach (H&E stain). b: Fundic mucosa. Many psammoma-like small particles are present in the lamina propria (H&E stain). c: Pyloric mucosa (H&E stain). d: Histochemical findings in the pyloric mucosa. In the serial section of c, surface mucous cells stain blue with galactose oxidase thionine Schiff reaction (GOTS) and pyloric gland cells stain brown with PCS (GOTS/PCS).

Figure 4.

8 weeks after inoculation of H. pylori. a: Erosion is observed. Small clusters of surface mucous cells protruded into the lumen. Dilated mucous gland and accumulation of lymphocytes are present in the submucosa. b: Mucins in the surface mucous cells and in the pyloric glands are depleted markedly. Surface mucous gel layer (SMGL) was thickened and consist of two type of gastric mucins. Thin strands of mucins from pyloric gland cells are evident and join the SMGL (GOTS/PCS). Figure 3. 4 weeks after inoculation of H. pylori. a: In the transitional zone between pylorus and fundus, elongated pseudopyloric glands emerge (H&E stain). b: Neutrophils infiltrate the epithelium and form intrafoveolar microabscess (H&E stain). c: H. pylori stained brown with immunostaining for H. pylori and are present in the surface mucous gel layer (immunoperoxidase method for H. pylori).

Figure 8.

52 weeks after inoculation of H. pylori. a: Dilated mucous glands are distributed in the lamina propria and submucosa (H&E stain). b: These mucous glands stain brown with PCS (GOTS/PCS). Figure 5. 26 weeks after inoculation of H. pylori. Ulcer is formed. Granulation tissue with inflammatory cells and necrotic materials are present in the ulcer base (H&E stain). Figure 6. 26 weeks after inoculation of H. pylori. Histological finding of the sessile polyps around the border between pylorus and fundus. Hyperplastic foveolae with widened stromal tissue are evident (H&E stain). Figure 7. 26 weeks after inoculation of H. pylori. a: Incomplete intestinal metaplasia is recognized. b: Metaplastic goblet cells show alcianophilia (AB/PAS stain).