Nishizaki Y, Guth P H, Kim G, Wayland H, Kaunitz J D
Medical Service, Wadsworth Veterans Affairs Medical Center, Los Angeles 90073.
Am J Physiol. 1994 Jul;267(1 Pt 1):G94-104. doi: 10.1152/ajpgi.1994.267.1.G94.
Stimulation of acid secretion is associated with enhanced resistance of the gastric mucosa to damage by luminal acid. We studied the mechanism by which gastric mucosal defenses are modulated in a system in which mucus gel thickness, intracellular pH (pHi), gastric mucosal blood flow, and acid secretion can be measured simultaneously in vivo, using a recently developed microfluorometric technique. Intravenous infusion of pentagastrin in a dose associated with maximal acid secretion increased mucus gel thickness, pHi, and mucosal blood flow during superfusion with a neutral solution. Subsequent superfusion with an acidic buffer (pH 1.7) further increased blood flow to nearly three times basal. During superfusion with luminal acid, pHi fell more slowly and recovered toward baseline more quickly in pentagastrin-infused rats than in controls. Pretreatment with the H2-receptor antagonist cimetidine abolished the increased blood flow associated with pentagastrin, impairing pHi homeostasis, although cimetidine increased mucus gel thickness in the absence of pentagastrin. We conclude that gastric defense mechanisms at the preendothelial and postepithelial levels are enhanced during acid secretion as part of a histamine-dependent homeostatic mechanism that balances gastric protective mechanisms with acid secretion. The net result of these enhanced defenses is the preservation of gastric surface cell pHi despite the presence of a large proton gradient between lumen and blood.
胃酸分泌的刺激与胃黏膜对腔内酸损伤的抵抗力增强有关。我们使用最近开发的微荧光测定技术，在一个能够同时在体内测量黏液凝胶厚度、细胞内pH值（pHi）、胃黏膜血流量和胃酸分泌的系统中，研究了胃黏膜防御机制的调节机制。静脉输注与最大胃酸分泌相关剂量的五肽胃泌素，在中性溶液灌注期间增加了黏液凝胶厚度、pHi和黏膜血流量。随后用酸性缓冲液（pH 1.7）灌注，进一步使血流量增加至基础水平的近三倍。在腔内酸灌注期间，与对照组相比，五肽胃泌素灌注大鼠的pHi下降更慢，向基线恢复更快。用H2受体拮抗剂西咪替丁预处理消除了与五肽胃泌素相关的血流量增加，损害了pHi的稳态，尽管西咪替丁在无五肽胃泌素的情况下增加了黏液凝胶厚度。我们得出结论，作为一种组胺依赖性稳态机制的一部分，在胃酸分泌过程中，内皮前和上皮后水平的胃防御机制增强，该机制平衡了胃保护机制与胃酸分泌。这些增强防御的最终结果是，尽管管腔和血液之间存在很大的质子梯度，但仍能维持胃表面细胞的pHi。
