Effect of Helicobacter pylori infection on Barrett's esophagus and esophageal adenocarcinoma formation in a rat model of chronic gastroesophageal reflux.
OBJECTIVE
To investigate the relationship between Helicobacter pylori infection and Barrett's esophagus (BE), a rat model of chronic gastroesophageal reflux with H. pylori infection was established and the degree of inflammation, incidence of BE and esophageal adenocarcinoma (EA) were evaluated.


METHODS
Eight-week-old male specific-pathogen-free SD rats were divided into five groups randomly: pseudo-operation group; esophagojejunum anastomosis (EJA) group; EJA with H. pylori infection group; EJA with H. pylori infection and celecoxib-treated group; EJA with celecoxib-treated group. Rats were kept for 30 weeks after surgery. Esophageal lesion was evaluated grossly and microscopically. The expression of COX-2 and CDX2 was determined by RT-PCR and immunohistochemistry staining. The level of PGE₂ was assessed by enzyme-linked immunosorbent assay.


RESULTS
Esophageal mucosal injury in the group of EJA with H. pylori infection was decreased than that in EJA group (p < .05). The incidence of BE and EA in rats undergoing EJA with H. pylori infection was increased than in rats undergoing EJA with no statistical difference. Celecoxib treatment decreased the incidence of EA in rats undergoing EJA with H. pylori infection (p < .05). The expression of CDX2 mRNA was decreased in rats with H. pylori infection or treated with celecoxib than in the rats of pseudo-operation group (p < .05). When compared with those in rats of pseudo-operation group, the expression of COX-2 mRNA and the level of PGE₂ were upregulated in rats undergoing EJA irrespective of H. pylori infection (p < .05) and downregulated in rats treated with celecoxib (p < .05). When H. pylori colonized in esophagus, the severity of inflammation and the incidence of BE and EA were increased significantly. Higher levels of COX-2 expression and PGE₂ were detected in rats with esophageal H. pylori colonization.


CONCLUSIONS
When H. pylori infect in stomach, it may reduce the severity of inflammation. However, when colonizes in esophagus, H. pylori increases the severity of esophageal inflammation and the incidence of BE and EA. Celecoxib administration attenuates the incidence of EA by inhibiting COX-2 expression.
Department of Gastroenterology, Peking University First Hospital, Xicheng District, Beijing 100034, China.
Fang-Xun
FX
Liu
Wei-Hong
WH
Wang
Jing
J
Wang
Jiang
J
Li
Pei-Pei
PP
Gao
D000230:Adenocarcinoma / Q000473:pathology*; D000714:Anastomosis, Surgical; D000818:Animals; D001471:Barrett Esophagus / Q000150:complications* / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D000071616:CDX2 Transcription Factor; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000235:genetics; D015232:Dinoprostone / Q000032:analysis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000473:pathology*; D004947:Esophagus / Q000473:pathology; D020869:Gene Expression Profiling; D016481:Helicobacter Infections / Q000150:complications* / Q000473:pathology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006651:Histocytochemistry; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D008853:Microscopy; D011720:Pyrazoles / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics
D000071616:CDX2 Transcription Factor; C541055:Cdx2 protein, rat; D018398:Homeodomain Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D014157:Transcription Factors; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D000068579:Celecoxib; D015232:Dinoprostone