首页|Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa

Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa

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AIM:To evaluate the protective properties of novel prostone CIC-2 agonist SPI-8811 in porcine model of gastric acid injury.METHODS:Porcine gastric mucosa was mounted in Ussing chambers and injured by bathing mucosal tissues in an HCl Ringer's solution (pH =1.5) with or without SP1-8811 (1 μmol/L),cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor (inhibitor 172,10 μmol/L,apical) and CIC-2 inhibitor ZnCl2,300 μmol/L,apical),on the apical surface of tissues.Transepithelial resistance and mucosal-to-serosal 3H-mannitol fluxes were measured over a 90-min period.Tissues were analyzed by morph metric techniques,Immunofluorescence and by western blots.RESULTS:Compared with control tissues,acid exposure decreased transepithelial electrical resistance (TER)and increased 3H-mannitol flux.Pretreatment of gastric mucosa with SPI-8811 was protective against acidinduced decreases in TER (TER,50 Ω.cm2 vs 100 Ω'cm2)and abolished increases in flux (3H-mannitol flux,0.10 μmol/L.cm2 vs 0.04 μmol/L.cm2).Evidence of histological damage in the presence of acid was markedly attenuated by SPI-0811.Immunofluorescence and western analysis for occludin revealed enhanced localization to the region of the tight junction (TJ) after treatment with SPI-8811.Pretreatment with the CIC-2 inhibitor ZnCl2,but not the selective CFTR inhibitor 172,attenuated SPI-8811-mediated mucosal protection,suggesting a role for CIC-2.Prostone may serve both protective and reparative roles in injured tissues.CONCLUSION:CIC-2 agonist SPI-8811 stimulated enhancement of mucosal barrier function by protecting TJ protein occludin in porcine gastric mucosa and thus protected the gastric acid injury in porcine stomach.

StomachMucosal permeabilityCIC-2 chloride channelTight junction

Meghali Nighot、Adam Moeser、Ryuji Ueno、Anthony Blikslager

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Departments of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, United States

Departments of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, United States

Departments of Sucampo Pharmaceuticals, Inc.,Bethesda, MD 20810, United States

2012

10.3748/wjg.v18.i34.4684

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子：1.001
ISSN：1007-9327
年,卷(期)：2012.18(34)
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