Mechanism by which Helicobacter pylori infection causes gastric ulcers Mongolian gerbils

本研究旨在阐明幽门螺杆菌（helicoboter pylori， H.pylori）诱发蒙古沙鼠胃溃疡的机制。一次口服接种VacA和caga阳性标准株（NCTC11637）幽门螺杆菌。幽门螺杆菌感染导致粘膜炎症，包括中性粒细胞浸润，与细胞因子诱导的中性粒细胞趋化剂（CINC）表达有关。此后，眼底出现出血性病变，随后在同一区域产生溃疡。根除幽门螺杆菌可消除CINC表达和胃炎病变。奥美拉唑对胃酸分泌的抑制也改善了幽门螺杆菌诱导的胃病理，另一方面，幽门螺杆菌感染使溃疡前粘液合成受损，胃上皮细胞暴露于幽门螺杆菌后，粘液分泌明显减少。当胃炎变得严重时，诱导干扰素- γ (IIFNgamma)，并在幽门螺杆菌存在下对粘液分泌发挥有效的抑制作用。吲哚美辛抑制前列腺素（PG）的合成加速了幽门螺杆菌引起的胃溃疡，尽管该药物在正常动物中没有引起任何病变或溃疡。这些结果表明，CINC、中性粒细胞浸润、胃酸和IFNgamma在幽门螺杆菌引起的胃溃疡的产生中起有害作用，而胃粘液和pg在胃粘膜中起保护作用。

This study was designed to clarify the mechanism of Helicobocter pylori (H.pylori)-induced gastric ulcers in Mongolian gerbils. H.pylori of a VacA- and CagA-positive standard strain (NCTC11637) was once orally inoculated to the animals. H.pylori infection resulted in mucosal inflammation including neutrophil infiltration, associated with cytokine-induced neutrophil chemoattractant (CINC) expression. Thereafter, hemorrhagic lesions occurred in the fundus, followed by generation of ulcers in the same area. Eradication of H.pylori eliminated both CINC expression and gastritis with lesions. Inhibition of acid secretion by omeprazole also improved H.pylori-induced gastric pathology, On the other hand, H.pylori infection impaired mucus synthesis prior to ulceration, and exposure of gastric epithelial cells to H.pylori caused a marked decrease in mucus secretion. Interferon-gamma (IIFNgamma) was induced when gastritis became severe, and exerted a potent inhibitory effect on mucus secretion in the presence of H.pylori. Inhibition of prostaglandin (PG) synthesis by indomethcin accelerated H.pylori-induced gastric ulceration, although the drug did not cause any lesions or ulcers in normal animals. These results suggest that CINC, neutrophil infiltration, gastric acid and IFNgamma serve as deleterious factors in generation of H.pylori-induced gastric ulcers, while gastric mucus and PGs play protective roles in the gastric mucosa.