Immunohistological Study on a Fibronectin-related Substance in the Gastric Fundic Mucosa : On an Ethanol-induced Gastric Ulcer Model of the Rat

The pathogenetic role of fibronectin-related substance （FNRS）, which was immunohistologically identified mainly in the lower portion of the gastric fundic mucosa, was studied using an ethanol （EtOH）-induced gastric ulcer model of the rat. Macroscopic and microscopic changes occurred in the gastric mucosa immediately （usually within 5 minutes） and developed time-dependently after the ingestion of 100% EtOH. The FNRS in the fundic mucosa decreased similarly and time-dependently and could be hardly detected 60 minutes after the ingestion of 100% EtOH. The ulcer index（UI） increased and inversely the FNRS score decreased time-dependently, showing a mirror-image manner. 20% EtOH did not cause visible mucosal alterations, but the FNRS decreased with time. The latter changes, however, were observed to a lesser degree than those in both 50% and 100% EtOH groups. These gastric mucosal lesions, which were adjudged from macroscopic and histological changes, developed in a concentration-dependent manner for EtOH. The changes in UI and FNRS score appeared to show a mirror image. Pretreatment with either cimetidine （30 and 50 mg/kg, i. v.）, 11（R）, 16, 16-trimethyl prostaglandin E2 （tmPGE2; 10 and 50 μg/kg, p. o.） or sulfhydryl cysteamine （50 and 200 mg/kg, s. c. i.） significantly prevented macroscopic and microscopic changes in the gastric mucosa which were induced 60 minutes after the ingestion of 50% EtOH. These drugs significantly decreased the UI but increased the FNRS score, dose-dependently. These results indicate that the FNRS located in the lower portion of the fundic mucosa, in which acid and pepsin are actively secreted, plays a protective role in the pathogenesis of the EtOH-induced gastric ulcer of the rat. It is also suggested that the FNRS may be mediated by H2 receptor and/or endogenous PG.