GASTRIC MUCOSAL PERMEABILITY AND CYTOPROTECTION

最近，胃粘膜已被证明积极分泌碳酸氢盐（HCO 3-） 进入管腔。 这一观察结果导致了一种假设， HCO 3-可能是胃粘膜的另一重要细胞保护机制， 因为分泌的HCO 3-可能中和在细胞膜上的管腔内酸， 粘膜表面。 为了评估这一假设，拟议的研究设计 (1)为了评价HCO 3-分泌对胃肠道酸碱状态的作用， 通过测量壁内pH值和（2）检查粘膜的变化率， HCO 3-各种刺激后的分泌。 它们包括（1）乙酰水杨酸 酸，一种已知的胃刺激物，（2）前列腺素E2，一种细胞保护剂 抗实验性溃疡，和（3）缺血，一个诱发因素， 急性溃疡形成 此外，以下研究将确定HCO 3- 分泌受促分泌素如乙酰胆碱、组胺和 五肽胃泌素和/或cGMP介导。 这些研究的实验模型 将是体内犬胃，允许计算HCO 3- 通过测量胃内pCO 2和pH分泌，如Garner所述， 弗莱姆斯壮 这项技术将被添加到我们目前的测量能力， 胃血流量的γ标记微球，粘膜cGMP的 放射免疫分析和微电极技术测定壁内pH值。

Recently, gastric mucosa has been shown to actively secrete bicarbonate (HCO3-) into the lumen. This observation leads to a hypothesis that active secretion of HCO3- may be another important cytoprotective mechanism of the gastric mucosa, since the secreted HCO3-is likely to neutralize the intraluminal acid at the mucosal surface. To assess this hypothesis, the proposed studies are designed (1) to evaluate the role of HCO3- secretion on the acid-base status of the mucosa by measuring intramural pH and (2) to examine the changes in the rate of HCO3- secretion following various stimuli. They include (1) acetylsalicylic acid, a known gastric irritant, (2) Prostaglandin E2, a cytoprotective agent against experimental ulcerations, and (3) ischemia, a predisposing factor in acute ulcerogenesis. In addition, the following studies will determine if HCO3- secretion is affected by secretagogues such as acetylcholine, histamine and pentagastrin and/or mediated by cGMP. The experimental model for these studies will be an in vivo canine stomach which permits the calculation of HCO3- secretion by measuring intragastric pCO2 and pH as described by Garner and Flemstrom. This technique will be added to our present ability to measure gastric blood flow by gamma-labeled microspheres, mucosal cGMP by radioimmunoassay and intramural pH by the microelectrode technique.