Mechanism by which Helicobacter pylori infection causes gastric ulcers Mongolian gerbils

本研究旨在阐明幽门螺杆菌(H.Pylori)诱导沙土鼠胃溃疡的机制。将VacA和CagA阳性标准菌株(NCTC11637)的H.幽门螺杆菌感染引起粘膜炎症，包括中性粒细胞浸润，并与细胞因子诱导的中性粒细胞趋化因子(CINC)表达有关。此后，眼底出现出血性病变，随后同一区域出现溃疡。根除幽门螺杆菌可消除CINC的表达，消除有病变的胃炎。奥美拉唑抑制胃酸分泌也改善了幽门螺杆菌诱导的胃黏膜病理改变，另一方面，幽门螺杆菌感染可损害溃疡前的粘液合成，而胃上皮细胞暴露于幽门螺杆菌可使粘液分泌显著减少。干扰素-γ在胃炎加重时产生，在幽门螺杆菌感染时对粘液分泌有很强的抑制作用。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，尽管该药物不会在正常动物中引起任何损害或溃疡。提示CINC、中性粒细胞浸润、胃酸和IFN-γ在Hp诱导的胃溃疡的发生中起有害作用，而胃粘液和PGs对胃粘膜起保护作用。

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.