Preconditioning stress prevents cold restraint stress-induced gastric lesions in rats:: Roles of COX-1, COX-2, and PLA2
Preconditioning stress prevents cold restraint stress-induced gastric lesions in rats:: Roles of COX-1, COX-2, and PLA2
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DOI：
10.1007/s10620-006-9394-8
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发表时间：
2007-02-01
影响因子：
3.1
通讯作者：
Takeuchi, Koji
中科院分区：
文献类型：
--
作者：
Tanaka, Akiko;Hatazawa, Ryo;Takeuchi, Koji
我们研究了轻度应激对冷束缚应激所致胃损伤的保护作用，特别是对前列腺素(PGs)/环氧合酶(COX)同工酶的保护作用。大鼠暴露于重度应激(10℃冷束缚应激6h)或轻度应激(10℃冷束缚应激30min，常温60min)，然后进行重度应激。严重的应激导致胃部损伤，并伴随着体温的降低。阿托品可抑制溃疡反应，消炎痛和SC-560可加重溃疡反应，但罗非昔布不能，尽管这些药物对BT的改变没有任何影响。轻度应激可抑制重度应激引起的胃溃疡和BT下降，这些作用可被COX-1和COX-2抑制剂逆转。重度应激后4小时，胃组织COX-2表达上调，轻度应激略有加速作用。COX-2在正常和应激状态下的下丘脑也有表达。喹卡林(磷脂酶A(2)抑制剂)减弱了轻度应激对溃疡的保护作用，并减弱了重度应激引起的BT下降。低剂量的TA-0910(TRH类似物)也能预防严重应激所致的胃溃疡和BT的降低。这些结果表明，轻度应激对冷束缚应激诱导的胃溃疡具有保护作用，这种作用是由COX-1和COX-2产生的PG通过激活磷脂酶A(2)而外周和中枢介导的。TRH也可能参与温和应激的保护作用，可能是通过调节产热系统。
We investigated the protective effect of mild stress on gastric lesions induced by cold-restraint stress, especially concerning prostaglandins (PGs)/cyclo-oxygenase (COX) isozymes. Rats were exposed to severe stress (cold-restraint stress at 10 degrees C for 6 hr) or mild stress (cold-restraint stress at 10 degrees C for 30 min and kept at room temperature for 60 min) followed by severe stress. Severe stress induced gastric lesions, with a concomitant decrease in body temperature (BT). The ulcerogenic response was inhibited by atropine but worsened by indomethacin and SC-560 but not rofecoxib, although none of these agents had any effect on the change in BT. Mild stress suppressed the gastric ulceration and the decrease in BT induced by severe stress, and these effects were reversed by both COX-1 and COX-2 inhibitors. The expression of COX-2 in the stomach was up-regulated from 4 hr after severe stress and this response was slightly expedited by mild stress. COX-2 was also expressed in the hypothalamus under normal and stressed conditions. Quinacrine (phospholipase A(2) inhibitor) attenuated the protective effect of mild stress on the ulceration and decrease in BT caused by severe stress. TA-0910 (TRH analogue) at a low dose also prevented the gastric ulceration and the decrease in BT induced by severe stress. These results suggest that mild stress protects against cold-restraint stress-induced gastric ulceration, and the effect is peripherally and centrally mediated by PGs derived from both COX-1 and COX-2 through the activation of phospholipase A(2). TRH may also be involved in the protective effect of mild stress, probably through regulation of the thermogenic system.