Effect of PAF receptor antagonist on PGE2 content and COX-2 expression in gastric mucosa of young rats with endotoxemia / 解放军医学杂志

ABSTRACT

Objective To investigate the protective effect of prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2) and platelet activating factor (PAF) receptor antagonist on endotoxin-induced acute gastric mucosal injury in young rats. Methods Eighteen-day old Wistar rats were randomly divided into 4 groups normal control group, model group (LPS group), PAF antagonist prevention group, and PAF antagonist treatment group. The model of endotoxemia in young rats was reproduced by intraperitoneal injection of endotoxin (5mg/kg of O55B5 lipopolysaccharide). The rats in PAF prevention and treatment group received PAF antagonist BN52021 (Ginkgolide B, 5mg/kg) 0.5h before or after modeling. The rats in control group were given intraperitoneal injection of same amount of normal saline (1ml/kg). The animals were sacrificed 1.5, 3, 6, 24, 48 and 72h after intraperitoneal injection of endotoxin (8 in each group). The pathologic changes in gastric mucosa were observed after HE staining. The content of PGE2was measured by radioimmunoassay, the expression of COX-2 protein was determined by immunohistochemistry SP method, and the expression of COX-2 mRNA was assessed with RT-PCR method. Results Pathological changes in gastric mucosa were found to be edema of epithelial cells at 1.5h, and hyperemia and edema 3h after intraperitoneal injection of endotoxin in LPS group. The changes were most marked at 6h, including bleeding, karyorrhexis, pyknosis and apoptosis of epithelial cells of gastric mucosa. Exfoliation of the epithelium and neutrophil infiltration were observed at 24h, thinning of mucosa and a decrease in glands were observed at 48h, but no further changes were observed at 72h. However, all the above changes were significantly alleviated in prevention and treatment groups. The PGE2 content of gastric mucosa was lowered at 3h (P<0.05), and it was lowest at 6h (P<0.01) after endotoxin injection in LPS group, and significant difference was found between LPS group and control group. The PGE2 content of gastric mucosa was obviously increased at 3h and 6h in prevention group (P<0.05), and at 6h in treatment group (P<0.05). The differences at 6h were significant (P<0.01) among prevention group, treatment group and LPS group. No expression of COX-2 protein or mRNA was seen in gastric mucosal tissue of control group. In contrast with control group, cytoplasm COX-2 protein of gastric mucosal tissue was seen to express at 6h after endotoxin injection in LPS group, and it was obviously enhanced at 24, 48 and 72h (P<0.01), and the COX-2 mRNA level was also elevated. The expressions of COX-2 protein and mRNA were increased obviously at 6h in PAF antagonist prevention group and treatment group (P<0.01). The expressions of COX-2 protein at 6h and COX-2 mRNA at 24h were obviously elevated in prevention group and treatment group compared with those of LPS group (P<0.01). Conclusion PAF receptor antagonist may up-regulate the expression level of COX-2 protein and mRNA, increase PGE2 content, alleviate acute gastric mucosal injury, and promote the healing of gastric mucosal injury.