Filaretova L P, Bagaeva T R, Morozova O Iu
Ross Fiziol Zh Im I M Sechenova. 2012 Dec;98(12):1555-66.
The stress response involves the activation of two corticotropin-releasing factor (CRF) receptors types 1 and 2. The pituitary type 1 CRF receptors represent the primary receptors to activate the hypothalamic-pituitary-adrenocortical axis and, consequently, glucocorticoid production. Exogenous CRF induces an increase in glucocorticoid production and may protect the gastric mucosa against stress-induced injury. Here we examined contribution of glucocorticoids and CRF receptors type 2 to gastroprotective effect of exogenous CRF. Gastric injury was induced by 3 him-mobilization (at 10 degrees C) in conscious rats or 3.5 h gastric ischemia-reperfusion in anaesthetized rats. Intraperitoneal administration of CRF at the doses of 1.25 or 2.5 Mg/kg increased plasma corticosterone levels and suppressed the occurrence of gastric erosion induced by each stimulus. Metyrapone injected before CRF caused an inhibition of CRF-induced corticosterone response and prevented the protective effect of CRF on the gastric mucosa against erosion caused by immobilization (at 10 degrees C). However, metyrapone injection did not influence the protective effect of CRF on the gastric mucosa against ischemia-reperfusion-induced lesion. The protective effect of CRF on the gastric mucosa against ischemia-reperfusion-induced lesion was prevented by the nonselective CRF receptor antagonist astressin and selective type 2 CRF receptor antagonist astressin2-B. The results obtained suggest that exogenous CRF may protect the gastric mucosa against injury through involvement of glucocorticoids and also through CRF receptors type 2.
应激反应涉及两种促肾上腺皮质激素释放因子(CRF)受体1型和2型的激活。垂体1型CRF受体是激活下丘脑-垂体-肾上腺皮质轴从而促进糖皮质激素分泌的主要受体。外源性CRF可导致糖皮质激素分泌增加,并可能保护胃黏膜免受应激诱导的损伤。在此,我们研究了糖皮质激素和2型CRF受体在外源性CRF胃保护作用中的贡献。通过在清醒大鼠中进行3小时束缚(10℃)或在麻醉大鼠中进行3.5小时胃缺血-再灌注诱导胃损伤。腹腔注射剂量为1.25或2.5μg/kg的CRF可提高血浆皮质酮水平,并抑制每种刺激诱导的胃糜烂的发生。在CRF注射前注射甲吡酮可抑制CRF诱导的皮质酮反应,并阻止CRF对胃黏膜免受束缚(10℃)引起的糜烂的保护作用。然而,注射甲吡酮并不影响CRF对胃黏膜免受缺血-再灌注诱导损伤的保护作用。非选择性CRF受体拮抗剂阿施他辛和选择性2型CRF受体拮抗剂阿施他辛2-B可阻止CRF对胃黏膜免受缺血-再灌注诱导损伤的保护作用。所得结果表明,外源性CRF可能通过糖皮质激素以及2型CRF受体参与保护胃黏膜免受损伤。