Evaluation and establishment of Mongolian gerbil model of long-term infection of Helicobacter pylori with highly-expressed thioredoxin-1 gene / 北京大学学报(医学版)

ABSTRACT

Objective:To establish a Mongolian gerbils model by long-term infection of Helicobacter py-lori (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 ger-bils were randomly divided into 3 groupsHp 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 War-thin-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-ex-pressed 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 sig-nificance (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-ex-pressed Trx1 gene group.The uninfected control animals showed no abnormal findings throughout the en-tire observation period.Conclusion:Hp with highly-expressed /lowly-expressed Trx1 gene colonizes stab-ly 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 gas-tric mucosa and the occurrence of gastric adenocarcinoma.Trx1 maybe the virulence factor that partici-pates in the pathogenesis of gastric cancer and Hp expressing high levels of Trx1 should be highly toxic for gastric diseases in China.