Tanaka S, Guth P H, Paulsen G, Kaunitz J D
Medical Service, West Los Angeles VA Medical Center, CA 90073, USA.
Gut. 1996 Aug;39(2):164-71. doi: 10.1136/gut.39.2.164.
Antisecretory and bismuth compounds protect the gastric mucosa from injury resulting from non-steroidal anti-inflammatory drugs.
To study the mechanism underlying the gastroprotective effects of ranitidine bismuth citrate (GG311) in rats.
Indomethacin rat injury model and in vivo microscopy in which acid output, surface cell intracellular pH (pHi), gastric mucus gel thickness, and mucosal blood flow were measured simultaneously.
In injury studies, GG311 dose dependently protected against severe injury induced by indomethacin (60 mg/kg subcutaneously). In in vivo microscopic studies, indomethacin significantly decreased mucus gel thickness and increased the initial rate of acidification of gastric surface cells when the superfusate pH was lowered from 7.4 to 1.0, and impaired pHi during acid exposure. Indomethacin had no effect on mucosal blood flow or acid output. GG311 alone had no effect on gel thickness, blood flow, or pHi homeostasis during acid exposure, but improved the initial acidification rate and pHi during superfusion with pH 1.0 solutions in the presence of indomethacin. In separate experiments, indomethacin pretreatment considerably increased gastric mucus bismuth concentrations in rats given GG311.
The gastroprotective effect of GG311 against indomethacin induced gastric injury is associated with high and prolonged gastric mucus bismuth concentrations, which may impair proton permeation across the mucus gel.
抗分泌及铋化合物可保护胃黏膜免受非甾体抗炎药所致损伤。
研究枸橼酸铋雷尼替丁（GG311）对大鼠胃保护作用的机制。
采用吲哚美辛大鼠损伤模型及体内显微镜检查，同时测量胃酸分泌量、表面细胞内pH值（pHi）、胃黏液凝胶厚度及黏膜血流量。
在损伤研究中，GG311呈剂量依赖性地保护大鼠免受皮下注射吲哚美辛（60 mg/kg）所致的严重损伤。在体内显微镜研究中，当灌流液pH值从7.4降至1.0时，吲哚美辛显著降低黏液凝胶厚度并增加胃表面细胞的初始酸化速率，且在酸暴露期间损害pHi。吲哚美辛对黏膜血流量或胃酸分泌量无影响。单独使用GG311对酸暴露期间的凝胶厚度、血流量或pHi稳态无影响，但在吲哚美辛存在的情况下，用pH 1.0溶液灌流时可改善初始酸化速率及pHi。在单独的实验中，吲哚美辛预处理可显著增加给予GG311的大鼠胃黏液中的铋浓度。
GG311对吲哚美辛所致胃损伤的胃保护作用与胃黏液中高浓度且持久的铋有关，这可能会损害质子穿过黏液凝胶的渗透。
