Cyclooxygenase 2, pS2, inducible nitric oxide synthase and transforming growth factor alpha in gastric adaptation to stress.

Abstract

To determine the role of mucosal gene expression of cyclooxygenase 2 (COX-2), pS2 (belongs to trefoil peptides), inducible nitric oxide synthase (iNOS) and transforming growth factor alpha (TGFalpha) in gastric adaptation to water immersion and restraint stress (WRS) in rats. Wistar rats were exposed to single or repeated WRS for 4 h every other day for up to 6 d. Gastric mucosal blood flow (GMBF) was measured by laser Doppler flowmeter-3. The extent of gastric mucosal lesions were evaluated grossly and histologically and expressions of COX-2, pS2,iNOS and TGFalpha were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot. The damage to the surface of gastric epithelium with focal areas of deep haemorrhagic necrosis was induced by repeated WRS. The adaptative cytoprotection against stress was developed with activation of cell proliferation in the neck regions of gastric glands. The ulcer index (UI) in groups II, III and IV was markedly reduced as compared with group I (I: 47.23+/-1.20; IV: 10.39+/-1.18,P<0.01). GMBF significantly decreased after first exposure to WRS with an adaptive increasement of GMBF in experimental groups after repetitive challenges with WRS. After the 4th WRS, the value of GMBF almost restored to normal level (I: 321.87+/-8.85; IV: 455.95+/-11.81, P<0.01). First WRS significantly decreased the expression of pS2 and significantly increased the expressions of COX-2, iNOS and TGFalpha. After repeated WRS, pS2 and TGFalpha expressions gradually increased (pS2: I: 0.37+/-0.02; IV: 0.77+/-0.01; TGFalpha: I: 0.86+/-0.01; IV: 0.93+/-0.03, P<0.05) with a decrease in the expressions of COX-2 and iNOS (COX-2: I: 0.45+/-0.02; IV: 0.22+/-0.01; iNOS: I: 0.93+/-0.01; IV: 0.56+/-0.01, P<0.01). Expressions of pS2, COX-2, iNOS and TGFalpha showed regular changes with a good relationship among them. Gastric adaptation to WRS injury involves enhanced cell proliferation, increased expression of pS2 and TGFalpha, and reduced expression of COX-2 and iNOS. These changes play an important role in adaptation of gastric mucosa after repeated WRS.