Tanaka J, Yuda Y, Inouye S, Yamakawa T
Pharmacology Department Drug Research Laboratory, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Morooka-cho, Kohoku-ku, 222-8567, Yokohama, Japan.
Eur J Pharmacol. 2001 Jul 13;424(1):69-74. doi: 10.1016/s0014-2999(01)01119-0.
In a rat model of the ischemia-reperfusion with pylorus ligation, gastric ulcer was formed, although gastric acid secretion was reduced. When the polymorphonuclear leukocytes were inactivated in advance, gastric ulcer was not formed, but acid secretion was increased, indicating that gastric acid is not a cause of the ulcer formation in this model. The mechanism of gastric acid suppression accompanied by ischemia-reperfusion was examined in relation to the role of oxygen-free radicals in this rat model. Prior administration of superoxide dismutase did not modulate acid secretion, but N-nitro-L-arginine methyl ester (L-NAME) increased acid secretion. The action of L-NAME was antagonized specifically by L-arginine, but not by D-arginine. S-nitroso-N-acetylpenicillamine did not inhibit basal acid secretion but antagonized the action of L-NAME. Aminoguanidine increased significantly the gastric acid output that was suppressed by ischemia-reperfusion. When polymorphonuclear leukocytes were inactivated by treatment with their antibody, the gastric acid output recovered to the level in the pylorus-ligated rat without ischemia-reperfusion. These results suggested that nitric oxide (NO) produced by the infiltrated polymorphonuclear leukocytes plays an important role in the suppression of acid secretion induced by ischemia-reperfusion.
在幽门结扎的缺血再灌注大鼠模型中，尽管胃酸分泌减少，但仍形成了胃溃疡。当多形核白细胞预先失活时，未形成胃溃疡，但胃酸分泌增加，这表明胃酸不是该模型中溃疡形成的原因。在该大鼠模型中，研究了与缺血再灌注相伴的胃酸抑制机制与氧自由基作用的关系。预先给予超氧化物歧化酶并未调节胃酸分泌，但N-硝基-L-精氨酸甲酯（L-NAME）增加了胃酸分泌。L-NAME的作用可被L-精氨酸特异性拮抗，但不能被D-精氨酸拮抗。S-亚硝基-N-乙酰青霉胺不抑制基础胃酸分泌，但拮抗L-NAME的作用。氨基胍显著增加了被缺血再灌注抑制的胃酸分泌量。当用抗体处理使多形核白细胞失活时，胃酸分泌量恢复到未进行缺血再灌注的幽门结扎大鼠的水平。这些结果表明，浸润的多形核白细胞产生的一氧化氮（NO）在抑制缺血再灌注诱导的胃酸分泌中起重要作用。
