Suzuki H, Yanaka A, Muto H
Department of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
Am J Physiol Gastrointest Liver Physiol. 2000 Jul;279(1):G107-17. doi: 10.1152/ajpgi.2000.279.1.G107.
The present study was conducted to elucidate the mechanisms by which Helicobacter pylori (HP)-derived ammonia causes gastric mucosal injury. Intact sheets of guinea pig gastric fundic mucosae were incubated in Ussing chambers. Both the luminal and the serosal pH were kept at 7.4. Transmucosal potential difference (PD) and electrical resistance (R) were monitored as indices of mucosal integrity. Restitution was evaluated by recovery of PD, R, and transmucosal [(3)H]mannitol flux after Triton X-100-induced mucosal injury. The effects of luminal or serosal NH(4)Cl on function and morphology of uninjured or injured mucosae were examined. In uninjured mucosae, serosal NH(4)Cl induced more profound decreases in PD and R and more prominent vacuolation in gastric epithelial cells than did luminal NH(4)Cl. In contrast, luminal NH(4)Cl markedly inhibited restitution in injured mucosae and caused an extensive vacuolation in gastric epithelial cells, as did serosal NH(4)Cl. Transmucosal ammonia flux was greater in the injured than in the uninjured mucosae. These results suggest that 1) basolateral membrane of gastric epithelial cells is more permeable to ammonia than apical membrane and 2) luminal ammonia, at concentrations detected in HP-infected gastric lumen, retards restitution in injured mucosae.
本研究旨在阐明幽门螺杆菌（HP）产生的氨导致胃黏膜损伤的机制。将豚鼠胃底黏膜完整片置于Ussing chamber中孵育。管腔和浆膜的pH均保持在7.4。监测跨黏膜电位差（PD）和电阻（R）作为黏膜完整性指标。通过Triton X-100诱导黏膜损伤后PD、R和跨黏膜[³H]甘露醇通量的恢复来评估修复情况。检测管腔或浆膜NH₄Cl对未损伤或损伤黏膜功能和形态的影响。在未损伤黏膜中，与管腔NH₄Cl相比，浆膜NH₄Cl引起PD和R更显著降低，胃上皮细胞空泡化更明显。相反，管腔NH₄Cl显著抑制损伤黏膜的修复，并导致胃上皮细胞广泛空泡化，浆膜NH₄Cl也是如此。损伤黏膜的跨黏膜氨通量大于未损伤黏膜。这些结果表明：1）胃上皮细胞的基底外侧膜对氨的通透性高于顶端膜；2）在HP感染胃腔中检测到的浓度下，管腔氨会延迟损伤黏膜的修复。
