[The role of cyclooxygenase 2 and prostaglandin I2 in the development of portal hypertensive gastropathy].
キーワード
概要
OBJECTIVE
To study the role of cyclooxygenase 2 (COX 2) and prostaglandin I2 (PGI2) in the development of portal hypertensive gastropathy (PHG).
METHODS
Forty Wistar rats were divided into surgery group (32) and control group (8). Partial portal vein ligation method was used to narrow the sectional area of portal vein to establish the experimental model of PHG in surgery group rats. Then they were divided into four groups (8 rats in each). The free pressure of portal vein was determined at the 1st, 2nd, 3rd, 4th weeks after the operation, and 8 rats were killed to observe the pathological change of gastric mucosa. The levels of 6-keto-PGF1 alpha, a stable metabolite of PGI2, were determined by radioimmunoassay in gastric mucosa homogenate and the blood of portal vein. The expression of COX 2 in gastric mucosa was determined by immunohistochemistry.
RESULTS
The free pressure of portal vein increased rapidly after partial portal vein ligation and maintained a high stable level after 1 week. They were (2.40+/-0.15) kPa, (2.38+/-0.17) kPa, (2.52+/-0.21) kPa, and (2.46+/-0.17) kPa at the 1st, 2nd, 3rd, and 4th weeks after partial portal vein ligation, while it was (0.90+/-0.16) kPa in control group (t>or=17.356, P<0.05). The gastric mucosa appeared pale, edema, hyperaemia, surface erosion, punctate hemorrhage and these lesions were more apparent with the time after the operation. The pathological examination showed that the gastric mucosa and submucosa thickened. The vessels of gastric mucosa and submucosa expanded and increased. There were lymphocytes and neutrophils infiltration around the vessels in the gastric mucosa and submucosa. The 6-keto-PGF1 alpha levels in gastric mucosa and the blood of portal vein increased rapidly and maintained a high level after partial portal vein ligation,which were higher than those in control group (104.52pg/ml+/-25.11pg/ml vs 73.62pg/ml+/- 20.33pg/ml, t=2.710, P<0.05; 180.21pg /ml+/-37.56pg /ml vs 142.11pg /ml+/-31.51pg /ml, t=2.198, P<0.05). The results of immunohistochemistry showed that the intensity and degree of the COX 2 staining in gastric tissue increased at the 1st, 2nd, 3rd, 4th weeks after partial portal vein ligation, while the COX 2 in control group rats was negative.
CONCLUSIONS
The expression of COX 2 and PGI2 in gastric tissue increased in portal hypertension. PGI2 as an inflammatory medium, damages the gastric mucosa by expanding vessels and other mechanisms in portal hypertension. It may be one of the important factors contributing to the development of PHG.
