Oates P J, Hakkinen J P
Pfizer Inc., Department of Metabolic Diseases, Groton, Connecticut.
Gastroenterology. 1988 Jan;94(1):10-21. doi: 10.1016/0016-5085(88)90604-x.
Concentrated ethanol causes gastric lesions by a mechanism that is poorly understood. We have investigated this mechanism in the rat stomach via gross morphologic, videomicroscopic, histochemical, and pharmacologic approaches. Within 1 min of contact, ethanol caused diffuse mucosal hyperemia. By 5 min, hyperemia greatly intensified at some mucosal sites. Beneath sites where mucosal hyperemia developed, intramural venules strongly constricted at 3-13 s postethanol, whereas submucosal arterioles dilated more than two times in diameter by 25 s. Submucosal venular constriction began sooner than arteriolar dilation (9 vs. 16 s, p less than 0.05). One-third of the gastric mucosal mast cells degranulated by 15 s postethanol; 50% discharged by 30 s. Ethanol-induced hyperemia was markedly reduced by lipoxygenase-selective inhibitors BW755C or nordihydroguaiaretic acid, or by the H1-antihistamine pyrilamine, but not by indomethacin, cimetidine, phentolamine, or methysergide. Based on these results, a model for the pathogenesis of ethanol-induced gastric lesions is proposed.
高浓度乙醇导致胃损伤的机制尚不清楚。我们通过大体形态学、视频显微镜、组织化学和药理学方法对大鼠胃中的这一机制进行了研究。接触乙醇1分钟内，胃黏膜出现弥漫性充血。5分钟时，部分黏膜部位充血明显加剧。在黏膜充血部位下方，壁内小静脉在接触乙醇后3 - 13秒强烈收缩，而黏膜下小动脉在25秒时直径扩张超过两倍。黏膜下小静脉收缩比小动脉扩张更早（9秒对16秒，p < 0.05）。三分之一的胃黏膜肥大细胞在接触乙醇后15秒脱颗粒；30秒时50%脱颗粒。脂氧合酶选择性抑制剂BW755C或去甲二氢愈创木酸，或H1 - 抗组胺药吡苄明可显著减轻乙醇诱导的充血，但吲哚美辛、西咪替丁、酚妥拉明或甲基麦角新碱则无此作用。基于这些结果，我们提出了乙醇诱导胃损伤发病机制的模型。
