Morris G P, Keenan C M, Shriver D A
Clin Invest Med. 1987 May;10(3):121-31.
This study was undertaken to investigate the ability of a cytoprotective synthetic primary alcohol PGE1 analog, rioprostil, to protect the rat gastric mucosa against topically applied 40% (v/v) ethanol. Use of an ex vivo gastric chamber model facilitated correlation of changes in dynamic physiological parameters (PD and net cation fluxes) with changes in mucosal structure. We were particularly interested in defining changes in mucosal structure which accompanied topical application of rioprostil and which might explain subsequent resistance to the effects of ethanol. Topical application of rioprostil for 10 min provided concentration-dependent protection against ethanol-induced hemorrhagic erosions. The most effective dose and concentration tested (25 micrograms rioprostil at a concentration of 10 micrograms/ml) completely prevented ethanol-induced lesion formation. Protection was not accompanied by significant preservation of the interfoveolar epithelium against ethanol, but did involve prevention of vasocongestion and limitation of damage to the superficial epithelium. Complete recovery of physiological parameters indicative of gastric mucosal barrier integrity occurred within 20 min. The most effective concentrations of rioprostil produced extensive subepithelial edema and, concurrently, significant increases in net efflux of sodium ions, decreases in mucosal PD, and loss of mucosal folding.
本研究旨在探讨一种具有细胞保护作用的合成伯醇前列地尔类似物利奥前列素保护大鼠胃黏膜免受局部应用40%（v/v）乙醇损伤的能力。使用离体胃腔模型有助于将动态生理参数（跨上皮电位差和净阳离子通量）的变化与黏膜结构的变化相关联。我们特别关注确定利奥前列素局部应用后伴随的黏膜结构变化，这些变化可能解释随后对乙醇作用的抗性。局部应用利奥前列素10分钟可提供浓度依赖性保护，防止乙醇诱导的出血性糜烂。测试的最有效剂量和浓度（浓度为10微克/毫升的25微克利奥前列素）完全防止了乙醇诱导的损伤形成。这种保护作用并非伴随着胃小凹间上皮对乙醇的显著保存，但确实包括预防血管充血和限制对浅表上皮的损伤。指示胃黏膜屏障完整性的生理参数在20分钟内完全恢复。利奥前列素的最有效浓度产生广泛的上皮下水肿，同时，钠离子净流出显著增加，黏膜跨上皮电位差降低，黏膜皱襞消失。
