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

胃酸抑制剂对幽门螺杆菌感染胃粘膜胃萎缩和胃癌发展的影响。

• 批准号: 10670450
• 负责人: YANAKA Akinori
• 金额: $ 1.86万
• 依托单位: UNIVERSITY OF TSUKUBA
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670450/
• 关键词: Helicobacter pylori; gastritis; gastric atrophy; ammonia; apoptosis; H2-receptor antagonist; proton pump inhibitor; Helicobacter pylori; プロトンポンプ阻害剤; 胃粘膜; 萎縮; 壁細胞; apoptosis

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.

目的：幽门螺杆菌(Hp)通过高尿素酶活力产生高氨。本研究旨在阐明氨破坏胃粘膜屏障功能，诱导胃上皮细胞凋亡的机制。方法：1.体外研究：(1)氨对小鼠胃粘膜上皮细胞株GSM06细胞凋亡的影响。(2)体外实验观察了氯化铵对完整胃底粘膜电生理和形态的影响。2.体内实验：观察Hp感染的C57/BL6小鼠长期应用酸性抑制剂(H2受体阻滞剂，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，其作用在高pH时增强；(2)NH4Cl降低胃粘膜细胞的电位差和阻力，并诱导胃腺细胞胞浆空泡化，尤以高腔pH时更为明显。体内研究：长期使用质子泵抑制剂或H2受体阻滞剂等酸抑制剂可加重胃炎和细胞凋亡，加速胃体萎缩，但对Hp阳性小鼠胃窦萎缩无明显影响。结论：长期抑酸可加重机体胃炎，促进胃腺细胞凋亡，加速机体萎缩，其机制可能与酸抑制过程中氨由NH4+转化为NH3有关。

项目成果

Hideo Suzuki, Akinori Yanaka, Hiroshi Muto.: "The mechanism of gastric mucosal apoptosis induced by ammonia."Ulcer Research. 27. 157-160 (2000)

Hideo Suzuki、Akinori Yanaka、Hiroshi Muto.：“氨诱导胃粘膜细胞凋亡的机制。”溃疡研究。

鈴木英雄,谷中昭典,武藤弘 他: "Helicobacter Pyloriによる胃粘膜上皮細胞傷害のメカニズム(第3報)"Ulcer Research. 26. 48-52 (1999)

Hideo Suzuki、Akinori Yanaka、Hiroshi Muto 等：“幽门螺杆菌引起的胃粘膜上皮细胞损伤的机制（第 3 次报告）” Ulcer Research 26. 48-52 (1999)。

谷中昭典,鈴木英雄,武藤弘 他: "胃酸分泌抑制剤の一長期投与p-H.prlori感染マウスにおける胃粘膜萎縮進展に及ぼす影響"胃分泌研究会誌. 32. 47-50 (2000)

Akinori Yanaka、Hideo Suzuki、Hiroshi Muto 等人：“长期服用胃酸分泌抑制剂对感染 p-H.prlori 的小鼠胃粘膜萎缩进展的影响”胃分泌研究学会杂志 32。 47-50 (2000)

Hideo Suzuki, Akinori Yanaka, Hiroshi Muto.: "Effects of ammonia and monochloramine on gastric mucosal barrier at different luminal pH."Ulcer Research. 26. 48-52 (1999)

Hideo Suzuki、Akinori Yanaka、Hiroshi Muto.：“不同腔内 pH 值下氨和一氯胺对胃粘膜屏障的影响。”溃疡研究。

鈴木英雄、谷中昭典、武藤弘: "HPによる胃粘膜上皮細胞傷害のメカニズム(第3報)-胃内のアルカリ環境下におけるアンモニア及びフリーラジカルの役割"Ulcer Research. 26.1. 48-52 (1999)

Hideo Suzuki、Akinori Yanaka、Hiroshi Muto：“HP 诱导的胃粘膜上皮细胞损伤的机制（第 3 次报告）——氨和自由基在胃碱性环境中的作用”，溃疡研究 26.1（1999）。