The Expression Of ICAM-1 In Indomethacin-Induced Acute Gastric Mucosal Injury In Rats And Its Significance

Objective: To investigate the mechanism of NSAID-induced acute gastric mucosal injury in children rats and to determine the effects of the dose and treatment time of indomethacin on gastric mucosal injury; To investigate the expression of Intercellular adhesion molecule- 1 in NSAID-induced acute gastric mucosal damage in rat and its role.Methods: (1)Different doses of indomethacin solution (5mg/kg, 10 mg/kg, 20 mg/kg,40mg/kg) were adminstered orally to rats. All rats were sacrificed after 3 hours' treatment . Measurement of gastric mucosal lesion index were performed. (2)Rats were orally adminstered with indomethacin solution at the dose of 20 mg/kg body weight. All rats were killed after 1, 3, 6, 12 and 24 hours' treatment . Measurement of gastric mucosal lesion index, quanlity of 6-keto-PGF1 ? , TXB2 in gastric mucosal and circulating neutrophil counts were performed . The expression of intercellular adhesion molecule- 1 in gastric mucosal was performed by immunohistochemistry staining.Results: (1)Liner haemorrhagic lesion,erosion and little ulcer was found in the gastric antrum macroscopically. There was a dose-response relationship between the dose range from 0 to 20mg/kg body weight of indomethac and gastric mucosal lesion index, but at the dose of 40 mg/kg body weight could not enhanced the gastric mucosal lesion .(2) Gastric mucosal lesion index reached the peak at 3h after indomethacin adminstration. The inhibition of synthsis of 6-keto-PGFl ? and TXB2was 84% and 87% respectively at 3h after indomethacin adminstration. There was a significant correlation between gastric mucosal lesion index and inhition of synthsis of cytoprotective prostaglandins.The injury maitained over 24 hours. There was no change of circulating neutrophil counts before treatment and at several time point of posttreatment. The expression of intercellular adhesion molecule- 1 in gastric vascular endothelial cell and epithelium cell peaked at at 1h , decreased slowly at 3h, until 24h after indomethacin adminstration. The time of expression of intercellular adhesion molecule- 1 was earlier than that of gastric mucosal injury in gastric mucosa.Conclusion: Indomethacin-induced gastric mucosal damage were observed. The damage was dependent of the dose of indomethacin at the range from 0 to 20 mg/kg body weight and the damage reached a maximum at 3 hours post indomethacin adminstration. Inhibition of synthsis of cytoprotective prostaglandins is the major mechanism of NSAID-assoiated gastric mucosal damage. It is suggest that the expression of intercellular adhesion molecule- 1 participate the mechanism of NSAID-induced acute gastric mucosal damage and plays an important role in the gastropathy .