Effects Of Teprenone On Expression Of Tight Junction Associated Proteins In Patients With Portal Hypertensive Gastropathy

Portal hypertensive gastropathy(PHG) is a common complication ofcirrhotic portal hypertension. PHG is clinically important because it may causeacute upper gastrointestinal bleeding in patients with portal hypertension. Itsimportance is second only to esophageal varices. The gastric microcirculationin PHG is abnormal. The gastric mucosal blood flow is decreased. The mucosain PHG appears to be highly susceptible to injury, as it has been shown toexhibit impaired healing and mucosal defense.The tight junction (TJ) between adjacent epithelial cells is a keycomponent of the gastric mucosal barrier. The epithelial barrier assists in themaintenance of epithelial cell surface polarity. It prevents the diffusion ofsolutes, macromolecules, and microorganisms between apical and basolateraldomains, and provides high-resistance intercellular seals, preventingparacellular diffusion between cells. Epithelial barrier function is regulated inlarge part by the apical most intercellular junction referred to as the TJs whichcontain transmembrane proteins(occluding, claudin, and junctional adhesionmolecule) and cytoplasmic plaque proteins (the zonula occludens ZO-1, ZO-2and ZO-3, cingulin).These protein-protein interactions are important for themaintenance of epithelial barrier functions.Propranolol is a non-selective β-blocker. It has been used mostfrequently to treat acute bleeding. Its effects are predicated on reduction ofportal pressure and presumably gastric blood flow.Teprenone is a gastric mucosal protective drug used clinically to treatgastric ulcers and gastritis. It’s an inducer of HSP72, which has a protectiveeffect against gastric mucosal injury. It can also stimulate prostaglandin, whichsuggests a potential role in the treatment of portal hypertensive gastricmucosal abnormalities. Therefore, this study aimed to investigate the role of tight junctionassociated protein in patients with portal hypertensive gastropathy and toevaluate the role of propranolol and teprenone in treatment of portalhypertensive gastropathy.Objective: This study investigates the molecular mechanisms of gastricmucosal barrier injury in patients with portal hypertensive gastropathy andevaluates the role of propranolol and teprenone in treatment of portalhypertensive gastropathy.Methods: Ten patients with portal hypertensive gastropathy wererandomly divided into two groups. After the Endoscopic biopsy, one of thegroups was treated with propranolol (30mg/day) only, while the other groupwas treated with both propranolol (30mg/day) and teprenone (150mg/day).Both groups were treated with these drugs for one month. The biopsy wouldbe taken again after one month, while the changes in the gastric mucosa ofthese patients would be observed. Another ten healthy volunteers were dividedinto a control group. The expression of the TJ proteins occludin and ZO-1inthe gastric epithelium was evaluated by immunohistochemistry.Results:①We could observe an abnormality of the gastric mucosadescribed as a mosaic-like pattern resembling ‘snake-skin’ in the patients withPHG. The gastric lesions were improved after treatment in bothgroups.②Histological examination showed that there were significantvascular ectasia of the mucosal and submucosal veins and capillaries in thepatients with PHG. After the treatment with propranolol and teprenone, theseverity of vascular ectasia has decreased. And the decreasing of the severityof vascular ectasia was more significant in the group treated with bothpropranolol and teprenone than in the group treated with propranololonly.③T he results of the expression of the TJ proteins occludin and ZO-1evaluated by immunohistochemistry showed that patients with PHG presentedsignificantly reduced expression of occludin and ZO-1as compared to controls(P <0.001, respectively). After the treatment with propranolol and teprenone,the expression of occludin and ZO-1increased in both groups(in the group treated with propranolol only, P <0.01, respectively);(in the group treatedwith both propranolol and teprenone, P <0.001, respectively).And the grouptreated with both propranolol and teprenone had a more significant increase ofthe expression of occludin and ZO-1(P <0.01, respectively).Conclusions: The expression of occludin and ZO-1significantly reducedin patients with PHG. This may be associated with the gastric mucosal barrierinjury in patients with PHG. Teprenone may restore the gastric mucosal barrierby increasing the expression of occludin and ZO-1in the gastric epithelium.