Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Japan.
J Pharmacol Sci. 2010;112(1):25-32. doi: 10.1254/jphs.09r11fm.
Ammonia is one of the important toxins produced by Helicobacter pylori (H. pylori), the major cause of peptic ulcer diseases. We examined whether glutamine or marzulene (a gastroprotective drug containing 1% sodium azulene and 99% glutamine) protects the gastric mucosa against H. pylori in vivo and investigated the mechanism underlying glutamine-induced mucosal protection against ammonia in gastric epithelial cells in vitro. Mongolian gerbils were fed for 3 months with a diet containing glutamine (2%-20%) or marzulene (20%) starting from 2 weeks or 2 years after H. pylori infection. Then, gastric mucosal changes were evaluated both macro- and microscopically. Cultured gastric epithelial cells were incubated in the presence of ammonia, with or without glutamine; and cell viability, ammonia accumulation, and chemokine production were determined. Gerbils exhibited edema, congestion, and erosion after 3-month infection; and after 2-year infection, they showed cancer-like changes in the gastric mucosa. Glutamine and marzulene significantly suppressed these pathological changes caused in the gastric mucosa by H. pylori infection. Ammonia was accumulated in the cells, resulting in an increase in chemokine production and a decrease in cell viability. These pathological responses were prevented by glutamine. In addition, glutamine decreased chemokine production and cell death through inhibition of cellular accumulation of ammonia, resulting in the prevention of H. pylori-induced gastric diseases in vivo. These results suggest that glutamine/marzulene would be useful for prophylactic treatment of H. pylori-induced gastric diseases in patients.
氨是幽门螺杆菌（H. pylori）产生的重要毒素之一，是消化性溃疡病的主要病因。我们研究了谷氨酰胺或马祖伦（一种含有 1%氮蓝烯和 99%谷氨酰胺的胃保护药物）是否能在体内保护胃黏膜免受 H. pylori 的侵害，并探讨了谷氨酰胺在体外诱导胃上皮细胞黏膜免受氨损伤的机制。蒙古沙土鼠在感染 H. pylori 后 2 周或 2 年开始，用含 2%-20%谷氨酰胺或 20%马祖伦的饮食喂养 3 个月。然后，从宏观和微观两个方面评估胃黏膜的变化。培养的胃上皮细胞在存在氨的情况下，用或不用谷氨酰胺孵育；并测定细胞活力、氨积累和趋化因子产生。感染 3 个月后，沙土鼠出现水肿、充血和糜烂；感染 2 年后，胃黏膜出现类似癌症的变化。谷氨酰胺和马祖伦显著抑制了 H. pylori 感染引起的胃黏膜的这些病理变化。氨在细胞内积累，导致趋化因子产生增加和细胞活力降低。谷氨酰胺可以预防这些病理反应。此外，谷氨酰胺通过抑制细胞内氨的积累，减少趋化因子的产生和细胞死亡，从而预防体内 H. pylori 引起的胃病。这些结果表明，谷氨酰胺/马祖伦可能对预防 H. pylori 引起的胃病有一定的治疗作用。
