Age-Related Changes in the Response of the Rat Gastric Mucosa to Acetic acid- and Indomethacin-induced Ulceration

Abstract

Reduced mucosal protection is known to occur in the gastrointestinal tract of older people. However, the understanding of the repair process in the injured stomach of the aged is low. In this study, the response of the gastric mucosa in rats of different ages to acetic acid and indomethacin induced ulcers were investigated. Male Wistar rats (aged 3, 6, 12 and 18 months) were divided into four groups according to their ages. Two experimental ulcer models- acetic acid (via intraluminal injection of 0.2 mL acetic acid into the glandular portion of the stomach for 45 seconds) and indomethacin (via 25mg/kg body weight of indomethacin, p.o) - were studied in each group. Indices of ulcer healing determined on days 3, 7, 14 and 21 post-induction were: ulcer area by planimetry, ulcer depth and width by histomorphometry, tissue regeneration by histology Gastric acid secretion was measured by continuous perfusion of the stomach with normal saline (1ml/minute) under a mixture of xylazine (0.0005ml/g b.w) and ketamine (0.0015ml/g b.w) anaesthesia (0.6 mg/100 g).. The percentage area of ulcerated stomach healed three days after acetic acid ulcer induction was 37.9, 28.0, 23.6 and 26.9 for the 3, 6, and 12 and 18 month old rats respectively. By day 21 total healing (100%) was observed in the 3month old rats while healing rates were 94.3%, 71.7% and 69.1% for the 6M, 12M and 18M rats respectively. Healing rate also decreased with age in the indomethacin ulcer model. Acid secretion rate declined with age. Significant reduction in acid secretion were observed in the later stage of the healing process and more prominent in younger than older rats. Histology revealed gastric ulceration in all groups on days 3 and 7 with presence of inflammatory cells at ulcer bed. By day 14, reduction in the inflammatory cells and greater fibroblast proliferation were observed in the 3 and 6-month but not in the 12- and 18-month old rats. The study provides experimental evidence for the delayed healing of gastric injury reported in old age.