Effects of acid inhibitors on progression of gastric atrophy and development of gastric cancer in Helicobacter pylori-infected gastric mucosa.

目的：幽门螺杆菌（Hp）通过高脲酶活性产生高浓度氨。本研究旨在阐明氨破坏胃黏膜屏障功能并诱导胃上皮细胞凋亡的机制。方法：1；体外实验：(1)研究氨（NH4Cl）对小鼠胃粘膜上皮细胞系GSM06细胞凋亡的影响。(2)体外观察NH4Cl对胃底粘膜完整片的电生理和形态学的影响。2. 体内研究：在感染Hp的C57/BL6小鼠中，研究了长期使用酸抑制剂（h2 -阻滞剂，PPI）对胃炎症和胃萎缩的影响。结果：1；体外实验(1)NH4Cl诱导GSM06细胞凋亡，且在高环境ph下作用增强；(2)NH4Cl降低了胃腺的电位差和抗性，并诱导胃腺细胞质空泡形成，特别是在高腔ph下。体内研究：长期使用酸抑制剂如质子泵抑制剂或h2阻滞剂会加重胃炎和细胞凋亡，加速体内萎缩，但在胃窦中没有，在hp阳性小鼠中没有，在hp阴性小鼠中没有。结论：在酸抑制过程中氨从NH4^+转化为NH3介导的hp感染胃体粘膜效应中，长时间的酸抑制可加重胃炎，促进胃腺凋亡，加速体萎缩。

Aims : H.pylori (Hp) produces high concentrations of ammonia by high urease activity. The present study was conducted to clarify the mechanisms by which ammonia disrupts gastric mucosal barrier function and induces apoptosis of gastric epithelial cells.Methods : 1. In vitro study : (1) Effects of ammonia (NH4Cl) on apoptosis of GSM06 cells, epithelial cell line derived from mice gastric mucosae were examined in vitro. (2) Effects of NH4Cl on electrophysiology and morphology of intact sheets of gastric fundic mucosae were examined in vitro. 2. In vivo study : Effects of prolonged use of acid inhibitors (H2-blocer, PPI) on gastric inflammation and gastric atrophy were examined in C57/BL6 mice infected with Hp.Results : 1. In vitro study (1) NH4Cl induced apoptosis of GSM06 cells, an effects augmented at high ambient pH.(2) NH4Cl decreased in potential difference and resistance, and induced cytoplasmic vacuolation in gastric glands especially at high luminal pH.2. In vivo study : Prolonged use of acid inhibitors such as proton pump inhibitors or H2-blockers exacerbated gastritis and apoptosis, accelerated atrophy in body, but not in antrum, in Hp-positive, but not in Hpnegative mice.Conclusions : Prolonged acid inhibition exacerbates body gastritis, enhances apoptosis of gastric gland, and accelerates body atrophy, in Hp-infected gastric body mucosa effects mediated by conversion of ammonia from NH4^+ to NH3 during acid inhibition.