Water-Immersion-Restraint Stress model in Mongolian gerbil forcomparison of pathoaenicity of Helicobacter pylori strains

Helicobacter pylori의 병원성 비교를 위한 gerbil의 수침구속스트레스 모델

  • Lee, Jin-Uk (Department of Laboratory Animal Sciences, College of Medicine, Seoul National University) ;
  • Kim, Ok-jiu (Department of Laboratory Animal Sciences, College of Medicine, Seoul National University)
  • 이진욱 (서울대학교 의과대학 실험동물학교실) ;
  • 김옥진 (서울대학교 의과대학 실험동물학교실)
  • Accepted : 2004.11.08
  • Published : 2004.12.30

Abstract

Helicobacter pylori (H. pylori)-infection is an important pathogen of stomach cancer after chronic gastritis and ulceration in the stomach and duodenum. However, the virulences of H. pylori strains have not been well-defined between clinical isolates. This study was designed to establish water-immersion-restraint stress (WIRS) model in mongolian gerbil for comparison of pathogenicity of H. pylori strains. To determine an optimal duration time for WIRS model in gerbil, 5-week-old Mongolian gerbils were divided into different groups by WIRS duration time. After graded duration of WIRS, the macroscopic ulcer index (UI) was measured with the stomach and duodenum of sacrificed animal. There were no significant differences between male and female in same duration group. However, the UI increased significantly in a time-dependent fashion. The group of 6 hours-WIRS animals showed severe hemorrhage and ulceration in their stomach and duodenum. On the other hand, the very mild lesions induced in 2 hours-treated animals. Therefore, we determined an optimal duration time for WIRS model in gerbil as 4 hours. Thereafter, we evaluated whether this WIRS model in gerbil could be used as an useful tool for in vivo comparison of pathogenicity of H. pylori strains by enhancement of pathological severity in H. pylori-infected gerbils. Mongolian gerbils were divided into H. pyloriinfected and PBS-inoculated groups. Thereafter, they were divided again into 4 hours-WIRS and no WIRS subgroups. After treatment, the severity of pathological changes was evaluated in a same manner with previous duration-determining experiment. When the animals were exposed to WIRS, the UI was significantly higher in the infected group than in the uninfected group. These results suggested that the established gerbil-WIRS model in this study enhanced effectively the severity of pathogenic changes in the H. pylori-infected Mongolian gerbils and could be used as an useful tool for in vivo comparison of pathogenicity of H. pylori strains.

Acknowledgement

Supported by : 인간생명과학연구단

References

  1. Figura, N., Guglielmetti, P., Rossolini, A., Barberi, A., Cusi, G., Musmanno, R. A., Russi, M. and Quaranta, S. Cytotoxin production by campylobacter pylori strains isolated from patients with chronic gastritis only. J. Clin. Microbiol. 1989, 27, 225-226
  2. Honda, S., Fujioka, T., Tokieda, M., Satoh, R, Nishizono, A. and Nasu, M. Development of Helicobacter pylori induced-gastric carcinoma in Mongolian gerbils. Cancer. Res. 1998, 58, 4255-4259
  3. Marshall, B. J. The future of Helicobacter pylori eradication: a personal perspective. Aliment. Pharmacol. Ther. 1997, 1(Suppl.), 109-115
  4. Newell, D. G. Virulence factors of Helicobacter pylori. Scand. J. Gastroenterol. Suppl. 1991, 187, 31-38
  5. Xiang, Z., Censini, S., Bayeli, P. F., Telford, J., Figura, N., Rppuoli, R. and Covacci, A. Analysis of expression of cagA and vacA virulence factor in 43strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that cagA is not necessary for expression of the vacuolatingcytotoxin. Infect. Immun. 1995, 63, 94-98
  6. Hansson, L. E., Nyren, O., Hsing, A. W., Bergstrom, R., Josefsson, S., Chow, W. H., Fraumeni, J. F. and Adami, H. O. The risk of stomach cancer in patientswith gastric or duodenal ulcer disease. N. Engl. J. Med. 1996, 335, 242-249
  7. Hahm, K. B., Lee, K. M., Kim, Y. B., Han, S. U. and Kim, M. W. Animal models of Helicobacter pylori infection. Korean J. Gastroenterol. 2001, 37, 399-405
  8. Ito, Y., Azuma, T., Ito, S., Miyazi, H., Hirai, M., Yamazaki, Y., Sato, F., Kato, T., Kohli, Y. and Kuriyama, M. Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter pylori isolated in Japan. J. Clin. Microbiol. 1997, 35, 1710-1714
  9. Spiegelhalder, C., Gerstenecker, B., Kerstem, A., Schiltz, E. and Kist, M. Purification of Helicobacter pylori superoxide dismutase and cloning and sequencing of the gene. Infect. Immun. 1993, 61, 5315-5325
  10. Eaton K. A., Morgan, D. R. and Krakowks, S. Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets.Infect. Immun. 1991, 59, 2470-2475
  11. Ho, S. A., Hoyle, J. A., Lewis, F. A., Secker, A. D., Cross, D., Mapstone, N. P., Dixon, M. F., Wyatt, J. I., Tompkins, D. S., Tayler, G. R. and Quirke, P. Direct polymerase chain reaction test for detection of Helicobacter pylori in humans and animals. J. Clin. Microbiol. 29, 2543-2549, 1991
  12. Takagi, K. and Okabe, S. The effects of drugs on the production and recovery processes of the stress ulcer. Jpn. J. Pharmacol. 1968, 18, 9-18
  13. Jung, T. S., Kang, S. C., Choi, Y. J., Jeon, B. S., Park, J. W., Jung, S. A., Song, J. Y., Choi, S. H., Park, S. G., Choe, M. Y., Lee, B. S., Byun, E. Y., Baik, S. C., Lee, W. K., Cho, M. J., Youn, H. S., Ko, G. H. and Rhee, K. H. Two-dimensional gel Electrophoresis of Helicobacter pylori for Proteomic Analysis. J. Korean Soc. Microbiol. 2000, 35, 97-108
  14. Tummuru, M. K. R., Cover, T. L. and Blaer, M. J. Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence for linkage to cytotoxin production. Infect. Immun. 1993, 61, 1799-1809
  15. Ahn, Y. O., Park, B. J., Yoo, K. Y., Kim, N. K., Lee, J. K., Ahn, H. S., Kang, D. H., Kim, H., Lee, M. S. and Park, T. S. Incidence estimation of stomach cancer among Koreans. J. Korean Med. Sci. 1991, 6, 7-14
  16. Marshall, B. J. and Warren, J. R. Unidentified curved bacilli in the stomach of patients with gastric and peptic ulceration. Lancet. 1984, 1, 1311-1315
  17. Baik, S. C., Kim, J. B., Cho, M. J., Kim, Y. C., Park, C. K., Ryou, H. H., Choi, H. J. and Rhee, K. H. Prevalence of Helicobacter pylori infection among normal Korean adults. J. Korean Soc. Microbiol. 1990, 25, 455-462
  18. Lee, S. H., Lim, C. Y., Lee, K. H., Yeo, S. J., Kim, B. J., Kim, S. J., Cho, M. J., Rhee, K. H. and Kook, Y. H. rpoB Gene analysis of Helicobacter pylori. J. Korean Soc. Microbiol 1999, 34, 401-408