Lee M, Aldred K, Lee E, Feldman M
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
Am J Physiol. 1992 Dec;263(6 Pt 1):G920-6. doi: 10.1152/ajpgi.1992.263.6.G920.
Aspirin, one of the most widely used drugs in the world, consistently produces gastric mucosal injury, but the pathogenic mechanisms are incompletely understood. The present study was designed to determine the role of neutrophils in aspirin-induced acute gastric mucosal injury. Gastric mucosal lesions induced by acidified aspirin (300 mg/kg) were completely prevented in rats that had been rendered profoundly neutropenic by anti-neutrophil serum. Aspirin-induced acute gastric mucosal lesions were also significantly, albeit incompletely, reduced in rats that had been rendered moderately neutropenic by methotrexate. Moreover, in the methotrexate-induced neutropenia model, the neutropenia-associated mucosal protection against aspirin-induced injury could be reversed by leucovorin rescue. Aspirin caused a marked and statistically significant reduction in gastric mucosal 6-ketoprostaglandin F1 alpha synthesis, but no significant changes in gastric mucosal leukotriene synthesis. Thus no gastric mucosal lesions were observed in profoundly neutropenic rats that were treated with aspirin, despite the marked inhibition of prostaglandin synthesis. These findings demonstrate that aspirin-induced acute gastric mucosal injury is a neutrophil-dependent process.
阿司匹林是世界上使用最广泛的药物之一，它始终会导致胃黏膜损伤，但其致病机制尚未完全明确。本研究旨在确定中性粒细胞在阿司匹林诱导的急性胃黏膜损伤中的作用。用抗中性粒细胞血清使大鼠严重中性粒细胞减少后，酸化阿司匹林（300mg/kg）诱导的胃黏膜损伤完全得到预防。在经甲氨蝶呤使大鼠中度中性粒细胞减少的情况下，阿司匹林诱导的急性胃黏膜损伤也显著减轻，尽管并不完全。此外，在甲氨蝶呤诱导的中性粒细胞减少模型中，与中性粒细胞减少相关的对阿司匹林诱导损伤的黏膜保护作用可通过亚叶酸解救而逆转。阿司匹林导致胃黏膜6-酮前列腺素F1α合成显著且有统计学意义地减少，但胃黏膜白三烯合成无显著变化。因此，尽管前列腺素合成受到明显抑制，但在用阿司匹林治疗的严重中性粒细胞减少大鼠中未观察到胃黏膜损伤。这些发现表明，阿司匹林诱导的急性胃黏膜损伤是一个依赖中性粒细胞的过程。
