Laboratory of Experimental Endocrinology, Pavlov Institute of Physiology, Russian Academy of Sciences, Russia.
J Physiol Pharmacol. 2009 Dec;60 Suppl 7:155-60.
Gastric ischemic preconditioning is one of the most effective approaches to attenuate the gastric mucosal injury caused by severe ischemia-reperfusion. In the present study we investigated whether glucocorticoid hormones participate in a realization of gastroprotective effect of ischemic preconditioning. Rats were exposed to prolonged gastric ischemia-reperfusion (30 min occlusion of celiac artery followed by 3 h of reperfusion) alone or with brief preliminary ischemic-reperfusion preconditioning (two 5 min episodes of occlusion of celiac artery followed by 10 min reperfusion). The experiments were carried out: 1) in adrenalectomized rats without or with corticosterone replacement and in sham-operated animals; 2) in rats pretreated by the inhibitor of glucocorticoid synthesis, metyrapone (30 mg/kg i.p.), and in control animals; 3) in rats pretreated by glucocorticoid receptors antagonist RU-38486 (20 mg/kg, p.o.) and in control animals. The prolonged ischemia-reperfusion resulted in the gastric injury. In control rats the brief ischemia-reperfusion (ischemic preconditioning) induced plasma corticosterone rise and attenuated the gastric lesions caused by prolonged ischemia-reperfusion. In adrenalectomized rats the gastroprotective effect of ischemic preconditioning was prevented but reversed by an acute corticosterone replacement (4 mg/kg, s.c.) applied immediately before ischemic preconditioning. Metyrapone pretreatment shortly inhibited corticosterone rise, caused by ischemic preconditioning, and prevented the gastroprotective action of ischemic preconditioning. The protective influence of ischemic preconditioning against gastric injury caused by prolonged ischemia-reperfusion was not observed in the rats pretreated by glucocorticoid receptors antagonist RU-38486. The results suggest that glucocorticoid hormones participate in a realization of the protective effects of ischemic preconditioning in gastric mucosa.
胃缺血预处理是减轻严重缺血再灌注引起的胃黏膜损伤的最有效方法之一。本研究探讨了糖皮质激素是否参与了缺血预处理的胃保护作用的实现。大鼠暴露于长时间的胃缺血再灌注（腹腔动脉闭塞 30 分钟，再灌注 3 小时）或短暂的初步缺血再灌注预处理（两次腹腔动脉闭塞 5 分钟，再灌注 10 分钟）。实验进行了：1）在肾上腺切除大鼠中，没有或用皮质酮替代，以及在假手术动物中；2）在经糖皮质激素合成抑制剂美替拉酮（30mg/kg，腹腔注射）预处理的大鼠中和在对照动物中；3）在经糖皮质激素受体拮抗剂 RU-38486（20mg/kg，口服）预处理的大鼠中和在对照动物中。长时间的缺血再灌注导致胃损伤。在对照大鼠中，短暂的缺血再灌注（缺血预处理）导致血浆皮质酮升高，并减轻了长时间缺血再灌注引起的胃损伤。在肾上腺切除大鼠中，缺血预处理的胃保护作用被阻止，但在缺血预处理前立即应用急性皮质酮替代（4mg/kg，皮下注射）可逆转。美替拉酮预处理可短暂抑制缺血预处理引起的皮质酮升高，并防止缺血预处理的胃保护作用。在经糖皮质激素受体拮抗剂 RU-38486 预处理的大鼠中，未观察到缺血预处理对长时间缺血再灌注引起的胃损伤的保护作用。结果表明，糖皮质激素参与了胃黏膜缺血预处理保护作用的实现。
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