Salt and stress synergize H. pylori-induced gastric lesions, cell proliferation, and p21 expression in Mongolian gerbils

Dig Dis Sci. 2007 Jun;52(6):1517-26. doi: 10.1007/s10620-006-9524-3. Epub 2007 Apr 3.

Abstract

Our aim was to determine if salt and stress enhance Helicobacter pylori (Hp) lesions in Meriones unguiculatus. Two hundred seventy-eight pathogen-free gerbils were allocated to seven groups: Hp-Sydney strain (45), 8% higher-salt diet (38), stress (60% space reduction/water immersion; 36), Hp + salt (33), Hp + stress (34), N-methyl-N-nitro-N-nitrosoguanidine (34), and sham (58). Gerbils were sacrificed at 1 week (67), 12 weeks (73), 52 weeks (65), and 68 weeks (73). Sydney, Padova, and Lauren classifications were blindly used. Proliferation, p53, p21, and apoptosis were assessed. Follicular active gastritis (grade 2/3) was observed in 10% of Hp gerbils, 38% of Hp + salt gerbils, and 29% of Hp + stress gerbils at 52 weeks and 67%, 83%, and 43% at 68 weeks (P < 0.05). Heterotopic proliferative glands were identified in synergy groups from 52 weeks, with increases in their number and size by 68 weeks. Higher proliferative rates were observed in Hp+salt gerbils (P < 0.0001), and p21 overexpression in Hp+salt and Hp+stress gerbils (both P's < 0.0001), by 68 weeks, without p53 increases. We conclude that salt and stress synergize Hp damage and increase pseudo-invasive gland foci.

MeSH terms

  • Animals
  • Cell Cycle / physiology
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Female
  • Gastric Mucosa / metabolism*
  • Gerbillinae
  • Helicobacter Infections / metabolism*
  • Helicobacter pylori
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Inflammation / metabolism
  • Precancerous Conditions / metabolism*
  • Sodium Chloride, Dietary / metabolism*
  • Specific Pathogen-Free Organisms
  • Stomach / pathology
  • Stress, Psychological / metabolism*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • Sodium Chloride, Dietary
  • Tumor Suppressor Protein p53