关键词: 硫氧还蛋白质类, 螺杆菌, 幽门, 胃肿瘤, 模型, 动物, 沙鼠亚科

Abstract:

Objective： To establish a Mongolian gerbils model by long-term infection of Helicobacter pylori (Hp) with highly-expressed thioredoxin-1 (Trx1) gene and to investigate the histopathological findings of gastric mucosa in Mongolian gerbils. Methods: In this study, 75 healthy male Mongolian gerbils were randomly divided into 3 groups: Hp with highly-expressed Trx1 gene group (n=30), Hp with lowly-expressed Trx1 gene group (n=30), and control group (n=15). The animals underwent gastric perfusion of Hp suspension once a week for 5 weeks. The animals were sacrificed at the end of 4, 20, 34, 48, 70, and 90 weeks after inoculation for detecting Hp colonization by rapid urease test and Warthin-Starry silver staining and histological examination, respectively. Results: (1) The Mongolian gerbil model of long-term infection of Hp with highly-expressed Trx1 gene and lowly-expressed Trx1 gene were successfully established. (2) The macroscopic mucosal lesions, including erythema, uneven, erosion, nodules, etc. could be observed in experimental groups. The severity of lesions and the time when lesions occurred in Hp with highly-expressed Trx1 gene group were heavier/earlier than that in Hp with lowly-expressed Trx1 gene group. (3) Histopathologically, the gastric mucosa of Hp with highly-expressed Trx1 gene group showed the mild dysplastic hyperplasia of epithelial cells 34 weeks after the Hp inoculation, and the time was in the 48th week in Hp with lowly-expressed Trx1 gene group. At the end of the 90th week after Hp inoculation, the gastric adenocarcinoma could be detected in the two experimental groups (71.4% vs. 42.8%). The difference between the two experimental groups did not reach statistical significance (P=0.592), which might be due to the small sample capacity and/or short observation time. In addition, there were 2 cases with severe epithelial dysplastic hyperplasia in Hp with highly-expressed Trx1 gene group, and only 3 cases with moderate epithelial dysplastic hyperplasia in Hp with lowly-expressed Trx1 gene group. The uninfected control animals showed no abnormal findings throughout the entire observation period. Conclusion: Hp with highly-expressed/lowly-expressed Trx1 gene colonizes stably in the glandular gastric mucosa of Mongolian gerbils. The histological changes after infection are similar to those of the Hp infected human being, and Hp with highly-expressed Trx1 gene cause the injury of gastric mucosa and the occurrence of gastric adenocarcinoma. Trx1 maybe the virulence factor that participates in the pathogenesis of gastric cancer and Hp expressing high levels of Trx1 should be highly toxic for gastric diseases in China.

Key words: Thioredoxins, Helicobacter pylori, Stomach neoplasms, Models, animal, Gerbillinae