Tarnawski A, Stachura J, Gergely H, Hollander D
Department of Veterans Affair Medical Center, Long Beach, California 90822.
Eur J Clin Invest. 1990 Aug;20(4):432-40. doi: 10.1111/j.1365-2362.1990.tb01881.x.
Exposure of the gastric mucosa to aspirin results in exfoliation of the surface epithelium and deep mucosal necrosis. We assessed the changes in the mucosal microvessels during aspirin-induced injury and arachidonic acid protection of the gastric mucosa using transmission electron microscopy. Male Sprague-Dawley rats received intragastric pretreatment with either solubilizer (control) or detergent solubilized arachidonic acid (148 mg kg-1). One hour later 1-ml suspension of 200 mg kg-1 body weight acidified aspirin was administered intragastrically. The ultrastructure of mucosal microvasculature was assessed at 15 min and 4 h after aspirin administration both qualitatively and quantitatively by determining the number of necrotic or damaged capillaries in standardized mucosal sections. In addition, mucosal specimens were immunostained with a specific antiserum against vimentin, an endothelial marker, and fluorescence intensity was measured with a Nikon FX microscopic photometric system. In control rats, aspirin produced significant damage to both superficial and deeper microvessels consisting of: rupture of capillary walls, necrosis of endothelial cells, damage to endothelial organelles, deposition of fibrin and adherence of platelets to damaged endothelium. Vimentin fluorescence was reduced three-fold. Microvascular injury preceded the development of deep necrotic lesions. Microvascular damage and deep mucosal necrosis were significantly reduced by arachidonic acid pretreatment. We conclude that gastric mucosal microvessels are the major target for aspirin-induced injury and arachidonic acid protection.
胃黏膜暴露于阿司匹林会导致表面上皮细胞脱落和深层黏膜坏死。我们使用透射电子显微镜评估了阿司匹林诱导的胃黏膜损伤过程中黏膜微血管的变化以及花生四烯酸对胃黏膜的保护作用。雄性Sprague-Dawley大鼠接受胃内预处理，分别给予增溶剂（对照组）或经去污剂溶解的花生四烯酸（148 mg/kg）。1小时后，给予200 mg/kg体重的酸化阿司匹林1 ml悬浮液灌胃。在阿司匹林给药后15分钟和4小时，通过测定标准化黏膜切片中坏死或受损毛细血管的数量，对黏膜微血管的超微结构进行定性和定量评估。此外，用针对波形蛋白（一种内皮标志物）的特异性抗血清对黏膜标本进行免疫染色，并用尼康FX显微镜光度系统测量荧光强度。在对照大鼠中，阿司匹林对浅表和深层微血管均造成了显著损伤，表现为：毛细血管壁破裂、内皮细胞坏死、内皮细胞器损伤、纤维蛋白沉积以及血小板黏附于受损内皮。波形蛋白荧光降低了三倍。微血管损伤先于深层坏死性病变的出现。花生四烯酸预处理可显著减轻微血管损伤和深层黏膜坏死。我们得出结论，胃黏膜微血管是阿司匹林诱导损伤和花生四烯酸保护的主要靶点。
