Mertz-Nielsen A, Eskerod O, Bukhave K, Rask-Madsen J
Department of Medical Gastroenterology, Hvidovre Hospital, Denmark.
Gut. 1995 Apr;36(4):511-5. doi: 10.1136/gut.36.4.511.
Prostaglandin analogues of the E-series theoretically offer the ideal antiulcer drugs. Peptic ulcer healing with prostaglandin analogues is, however, no better than would be predicted from their ability to inhibit gastric acid secretion and they are less effective than histamine H2 receptor antagonists in preventing ulcer relapse. It could be that prostaglandin analogues inhibit gastric mucosal synthesis or release of endogenous eicosanoids, thereby abrogating their own effects. This study, therefore, examined how a single therapeutic dose (200 micrograms) of misoprostol, a synthetic analogue of prostaglandin E1, influences gastric mucosal release of endogenous prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and chemotactic leukotriene B4 (LTB4) during basal conditions and in response to gastric luminal acidification (0.1 M HCl; 5 ml/min for 10 minutes). Nine healthy volunteers were studied in a single blind, cross over design. In each subject misoprostol or placebo was instilled in randomised order into the stomach, which was subsequently perfused with isotonic mannitol. Misoprostol significantly decreased basal as well as acid stimulated output of PGE2 and TXB2, without affecting output of LTB4. These data show that misoprostol inhibits gastric mucosal synthesis of prostanoids. Decreased concentrations, or even a changed profile, of native eicosanoids modulating the release of inflammatory mediators from immune cells might explain why prostaglandin analogues have a comparatively poor clinical performance in ulcer healing and prevention.
E 系列前列腺素类似物理论上可提供理想的抗溃疡药物。然而，用前列腺素类似物治疗消化性溃疡，其效果并不比根据其抑制胃酸分泌的能力所预测的更好，并且在预防溃疡复发方面，它们比组胺 H2 受体拮抗剂效果更差。可能是前列腺素类似物抑制了胃黏膜内源性类二十烷酸的合成或释放，从而消除了它们自身的作用。因此，本研究考察了单剂量治疗量（200 微克）的米索前列醇（一种前列腺素 E1 的合成类似物）在基础状态下以及对胃腔内酸化（0.1 M HCl；5 毫升/分钟，持续 10 分钟）的反应中，如何影响胃黏膜内源性前列腺素 E2（PGE2）、血栓素 B2（TXB2）和趋化性白三烯 B4（LTB4）的释放。采用单盲、交叉设计对 9 名健康志愿者进行了研究。在每个受试者中，将米索前列醇或安慰剂随机顺序灌入胃内，随后用等渗甘露醇进行灌注。米索前列醇显著降低了基础状态下以及酸刺激后的 PGE2 和 TXB2 的分泌量，而不影响 LTB4 的分泌量。这些数据表明米索前列醇抑制了胃黏膜前列腺素的合成。调节免疫细胞炎症介质释放的天然类二十烷酸浓度降低，甚至其谱型改变，可能解释了为什么前列腺素类似物在溃疡愈合和预防方面的临床效果相对较差。
