Reduction of ethanol-induced injury in portal hypertensive gastric mucosa of rats by induction of heat shock protein 72 by geranylgeranylacetone.

Portal hypertensive (PHT) gastropathy has an increased susceptibility to damage due to noxious factors. Heat shock protein (HSP) 72 has a protective effect against gastric mucosal injury and geranylgeranylacetone (GGA) is an inducer of HSP 72. However, it remains unclear how HSP 72 influences the PHT gastric mucosa. The aim of the present study was to investigate HSP 72 induction by GGA and the protective effect to gastric mucosa in PHT rats. PHT rats were produced by staged portal vein occlusion, and GGA 200 mg/kg was orally administered. Expression of HSP 72 protein in the gastric mucosa was evaluated by enzyme-linked immunosorbent assay, and gastric mucosal damage against 70% ethanol (10 mL/kg) following GGA or vehicle treatment was also estimated. Expression of mucosal HSP 72 after vehicle administration was significantly higher in the PHT rats compared with the sham-operated rats. After GGA treatment, portal pressure did not change but HSP 72 was significantly increased in the gastric mucosa of both groups. Ethanol-induced gastric mucosal damage was significantly decreased due to GGA treatment in the PHT rats, but not in the sham-operated rats. These findings suggest that HSP 72 expression is enhanced in PHT gastric mucosa and plays an important role in gastric mucosal protection. The induction of HSP 72 by GGA may therefore effectively prevent mucosal injury in the PHT stomach.