Filaretova Ludmila, Bagaeva Tatiana, Makara Gabor B
Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia.
Life Sci. 2002 Oct 11;71(21):2457-68. doi: 10.1016/s0024-3205(02)02078-7.
Our previous investigations suggest that the reduction of stress-induced corticosterone release, or inhibition of corticosterone actions, promotes stress-induced gastric erosions in rats. In this study the effect of glucocorticoid deficiency on susceptibility to gastric mucosal injury by nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated in rats. Gastric erosions induced in male rats by indomethacin (25 mg/kg sc) or acidified aspirin (40 mM po) were studied one week after adrenalectomy with or without corticosterone replacement or after occupation of glucocorticoid receptors by the antagonist RU-38486 during the period of erosion formation. Corticosterone for replacement (4 mg/kg sc) was injected 15 min before the administration of indomethacin or acidified aspirin to adrenalectomized rats. The antagonist RU-38486 (10 mg/kg po) was administered twice, 20 min before and 60 min after NSAID administration. Plasma corticosterone levels were measured by fluorometry. Gastric erosions were quantitated by measuring the area of damage. Indomethacin or acidified aspirin induced both plasma corticosterone rise and gastric erosions. Adrenalectomy decreased both basal and NSAID-induced corticosterone levels and markedly promoted gastric erosion formation caused by the NSAID. An acute corticosterone replacement mimicking indomethacin-and aspirin-induced corticosterone rise prevented the effect of adrenalectomy on the gastric erosions. The administration of the glucocorticoid/progesterone antagonist RU-38486 significantly potentiated the formation of gastric erosions induced by indomethacin as well as aspirin. These observations suggest a gastroprotective action of glucocorticoids released in response to NSAID treatment against NSAID-induced injury.
我们之前的研究表明，减轻应激诱导的皮质酮释放或抑制皮质酮的作用，会促进大鼠应激诱导的胃糜烂。在本研究中，评估了糖皮质激素缺乏对大鼠非甾体抗炎药（NSAIDs）所致胃黏膜损伤易感性的影响。在肾上腺切除术后一周，研究吲哚美辛（25 mg/kg皮下注射）或酸化阿司匹林（40 mM口服）诱导的雄性大鼠胃糜烂，术后分别给予或不给予皮质酮替代治疗，或者在糜烂形成期用拮抗剂RU-38486占据糖皮质激素受体。在给肾上腺切除的大鼠注射吲哚美辛或酸化阿司匹林前15分钟，注射用于替代的皮质酮（4 mg/kg皮下注射）。拮抗剂RU-38486（10 mg/kg口服）在NSAID给药前20分钟和给药后60分钟各给药一次。通过荧光测定法测量血浆皮质酮水平。通过测量损伤面积对胃糜烂进行定量。吲哚美辛或酸化阿司匹林均引起血浆皮质酮升高和胃糜烂。肾上腺切除术降低了基础和NSAID诱导的皮质酮水平，并显著促进了NSAID引起的胃糜烂形成。模拟吲哚美辛和阿司匹林诱导的皮质酮升高的急性皮质酮替代治疗可预防肾上腺切除术对胃糜烂的影响。给予糖皮质激素/孕酮拮抗剂RU-38486显著增强了吲哚美辛和阿司匹林诱导的胃糜烂形成。这些观察结果表明，NSAID治疗后释放的糖皮质激素对NSAID诱导的损伤具有胃保护作用。
