Takeuchi K, Ishihara Y, Okada M, Niida H, Okabe S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Jpn J Pharmacol. 1989 Feb;49(2):235-44. doi: 10.1254/jjp.49.235.
We assembled a new system using a lucite chamber and rat stomach for simultaneous measurement of transmucosal potential difference (PD) and luminal pH as indicators of the mucosal integrity and the secretory activity, respectively. The biological preparation involved only the glandular mucosa and responded to a variety of mucosal damaging agents by different degrees of PD reduction, pH increases and histological damages. When the mucosa was exposed for 10 min to 1 M NaCl, the reduced PD was restored with time, reaching the baseline values within 2 hr with histological restitution. Titration of gastric effluent showed that after the exposure, acid secretion ceased and a considerable amount of HCO3- was evident in the lumen, followed by re-secretion of acid. These secretory changes corresponded with those of luminal pH; this remained elevated for 1 hr after the exposure and returned to the basal values 2 hr later. The histological restitution as well as the PD recovery after damage were significantly interfered with by indomethacin (5 mg/kg, s.c.) or vasopressin (10 unit/kg/hr, i.v.), respectively, at the dose which inhibited the increased pH responses caused by 1 M NaCl or reduced the mucosal blood flow. These results suggest that this system may be useful for studying physiological changes of gastric mucosa after acute injury and for screening drugs that may have an effect on the repair process.
我们使用一个有机玻璃腔室和大鼠胃构建了一个新系统，用于同时测量跨黏膜电位差（PD）和腔内pH值，分别作为黏膜完整性和分泌活性的指标。生物制剂仅涉及腺黏膜，并且对多种黏膜损伤剂会有不同程度的PD降低、pH值升高和组织学损伤反应。当黏膜暴露于1 M NaCl 10分钟时，降低的PD会随时间恢复，在2小时内达到基线值，同时组织学也得以恢复。胃流出物的滴定显示，暴露后酸分泌停止，腔内出现大量HCO3-，随后酸重新分泌。这些分泌变化与腔内pH值的变化相对应；暴露后pH值在1小时内保持升高，2小时后恢复到基础值。吲哚美辛（5 mg/kg，皮下注射）或血管加压素（10单位/kg/小时，静脉注射）分别在抑制1 M NaCl引起的pH值升高反应或减少黏膜血流量的剂量下，显著干扰了损伤后的组织学恢复以及PD的恢复。这些结果表明，该系统可能有助于研究急性损伤后胃黏膜的生理变化，并用于筛选可能对修复过程有影响的药物。
