Konturek S J, Brzozowski T, Stachura J, Majka J
Institute of Physiology, University Medical School, Krakow, Poland.
Eur J Pharmacol. 1994 Feb 21;253(1-2):107-14. doi: 10.1016/0014-2999(94)90764-1.
Gastric mucosa adapts to ulcerogenic action of aspirin but the mechanism of this phenomenon is unknown. In this study, acute gastric lesions were produced by single or repeated oral administration of acidified aspirin in rats with intact or deactivated (by capsaicin) sensory nerves and with intact or suppressed synthase of nitric oxide (NO). Single oral dose of aspirin produced a dose-dependent increase in the area of gastric lesions accompanied by a significant increase in blood neutrophils, neutrophil infiltration into the mucosa, leukotriene B4 formation and almost complete suppression of prostaglandin synthesis. After repeated administration of aspirin, the mucosal damage progressively declined and this was accompanied by a significant augmentation in gastric blood flow. In addition, a reduction in blood neutrophil count, mucosal neutrophil infiltration and leukotriene B4 release was observed during this adaptation of the stomach to repeated aspirin insults. Capsaicin denervation of sensory nerves aggravated the damage induced by the first exposure of the stomach to aspirin and caused a significant reduction in gastric blood flow, but with repeated aspirin administration, gastric adaptation to this agent and a rise in gastric blood flow were observed. Pretreatment NG-nitro-L-arginine with (L-NNA), a specific inhibitor of nitric oxide synthase, eliminated the hyperemic response to repeated aspirin insults but failed to affect the adaptation to aspirin. We conclude that the rat stomach adapts readily to repeated aspirin insults despite sustained inhibition of prostaglandin biosynthesis and this adaptation appears to be mediated by a significant increase in gastric blood flow and a reduction in neutrophil activation and leukotriene B4 release.
胃黏膜能适应阿司匹林的致溃疡作用，但其机制尚不清楚。在本研究中，通过对感觉神经完整或失活（用辣椒素处理）以及一氧化氮（NO）合酶完整或受抑制的大鼠单次或重复口服酸化阿司匹林来制造急性胃损伤。单次口服阿司匹林会使胃损伤面积呈剂量依赖性增加，同时血液中性粒细胞显著增多、中性粒细胞浸润到黏膜、白三烯B4生成以及前列腺素合成几乎完全受到抑制。重复给予阿司匹林后，黏膜损伤逐渐减轻，同时胃血流量显著增加。此外，在胃适应重复的阿司匹林刺激过程中，观察到血液中性粒细胞计数、黏膜中性粒细胞浸润和白三烯B4释放减少。辣椒素使感觉神经去神经支配会加重胃首次接触阿司匹林所诱导的损伤，并导致胃血流量显著减少，但重复给予阿司匹林后，观察到胃对该药物产生适应性且胃血流量增加。用一氧化氮合酶的特异性抑制剂NG-硝基-L-精氨酸（L-NNA）预处理可消除对重复阿司匹林刺激的充血反应，但未能影响对阿司匹林的适应性。我们得出结论，尽管前列腺素生物合成持续受到抑制，但大鼠胃仍能轻易适应重复的阿司匹林刺激，这种适应性似乎是由胃血流量显著增加以及中性粒细胞活化和白三烯B4释放减少介导的。
