Ishikawa T, Sarfeh I J, Tarnawski A, Golshan R, Douglas T, Sugiyama M
Surgical Service, DVA Medical Center, Long Beach, CA 90822.
Surgery. 1992 Aug;112(2):341-6.
Epidermal growth factor (EGF) protects gastric mucosa against a variety of injurious agents, but the mechanism is unclear. Because the abnormal microvasculature of portal hypertensive (PHT) gastric mucosa is a major target of ischemia/reperfusion (I/R) injury, we used this model to assess EGF's protective role at the microvascular level.
Rats with PHT (staged portal vein ligation) received either EGF, 20 micrograms/kg, or saline solution intravenously, with or without indomethacin pretreatment (20 mg/kg subcutaneously). I/R was produced by withdrawing blood to systemic pressures of 30 mm Hg for 20 minutes and reinfusing it. Stomachs were excised 20 minutes later and evaluated for gross and histologic necrosis, microvascular permeability, mucosal ultrastructure and vimentin, and cyclooxygenase immunofluorescence.
In saline-treated rats, gross and histologic damage involved 46% +/- 3% of glandular mucosa and 23% +/- 3% of mucosal sections, respectively. Microvascular permeability was increased 43-fold over that of normal control rats. Vimentin immunofluorescence intensity was reduced to 36% +/- 4% that of normal control rats. EGF pretreatment reduced histologic necrosis to 2% +/- 1% (p less than 0.01). Microvascular permeability and vimentin intensity were almost normalized. Indomethacin partially reversed the mucosal protection induced by EGF.
EGF significantly reduces I/R injury to PHT gastric mucosa. Microvascular endothelia of PHT gastric mucosa are the major target of I/R injury and the site of EGF's protective action. Prostaglandins in part mediate EGF's protective action.
