Rebamipide attenuates indomethacin-induced gastric mucosal lesion formation by inhibiting activation of leukocytes in rats
Rebamipide attenuates indomethacin-induced gastric mucosal lesion formation by inhibiting activation of leukocytes in rats
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DOI：
10.1023/a:1018861818023
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发表时间：
1997-02-01
影响因子：
3.1
通讯作者：
Takatsuki, K
中科院分区：
文献类型：
--
作者：
Murakami, K;Okajima, K;Takatsuki, K
活化的白细胞释放的粒细胞弹性蛋白酶在白细胞浸润中发挥重要作用。由于活化的白细胞已被证明参与非甾体类抗炎药诱导的胃粘膜病变形成的发病机制，因此抑制活化的白细胞释放粒细胞弹性蛋白酶可能有助于预防这些病变。瑞巴派特是一种新型抗溃疡药，在体外可抑制活化的中性粒细胞释放粒细胞弹性蛋白酶。瑞巴派特和粒细胞弹性蛋白酶抑制剂ONO-5046显着抑制大鼠胃粘膜病变形成。给予吲哚美辛后3小时胃髓过氧化物酶活性显着增加。这种增加被瑞巴派特和 ONO-5046 显着抑制。西咪替丁不抑制活化的中性粒细胞释放粒细胞弹性蛋白酶。虽然西咪替丁显着阻止吲哚美辛引起的胃粘膜病变形成，但它并没有降低胃髓过氧化物酶的活性。因此，与西咪替丁不同，瑞巴派特可能通过抑制中性粒细胞活化来预防吲哚美辛诱导的胃粘膜病变形成。
Granulocyte elastase released from activated leukocytes plays an important role in leukocyte infiltration. Since activated leukocytes have been shown to be involved in the pathogenesis of gastric mucosal lesion formation induced by nonsteroidal antiinflammatory drugs, inhibition of granulocyte elastase release from activated leukocytes may be useful in the prevention of these lesions. Rebamipide, a novel antiulcer agent, inhibited granulocyte elastase release from activated neutrophils in vitro. Rebamipide and ONO-5046, a granulocyte elastase inhibitor, markedly inhibited gastric mucosal lesion formation in rats. Gastric myeloperoxidase activity was significantly increased 3 hr after indomethacin administration. This increase was significantly inhibited by rebamipide and ONO-5046. Cimetidine did not inhibit granulocyte elastase-release from activated neutrophils. Although cimetidine markedly prevented the indomethacin-induced gastric mucosal lesion formation, it did not reduce the gastric myeloperoxidase activity. Therefore, unlike cimetidine, rebamipide may prevent indomethacin-induced gastric mucosal lesion formation by inhibiting neutrophil activation.