Sun W H, Tsuji S, Tsujii M, Gunawan E S, Kawai N, Kimura A, Kakiuchi Y, Yasumaru M, Iijima H, Okuda Y, Sasaki Y, Hori M, Kawano S
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Japan.
J Pharmacol Exp Ther. 2000 Nov;295(2):447-52.
Recent studies indicate an expression of mitogen-inducible cyclooxygenase (COX-2) in gastric mucosa. Rebamipide, a mucoprotective agent enhances prostaglandin (PG) synthesis. The present study was designed to clarify the mechanism for rebamipide-induced mucosal protection. Male Sprague-Dawley rats were administered 5, 15, or 50 mg/kg/day rebamipide for 14 days. The expression of constitutive cyclooxygenase (COX-1) and COX-2 in gastric mucosa was determined using Western blot analysis. Another series of rats was used to examine 1) the levels of PGE(2) in stomach with and without pretreatment with a COX-2 inhibitor; 2) the protective action of rebamipide against gastric damage caused by 0.6 N HCl; and 3) the effects of a COX-2 inhibitor on rebamipide-induced gastric mucosal protection. COX-2 expression was enhanced, whereas COX-1 expression did not change significantly in the gastric mucosa of rats after treatment with rebamipide. The gastric mucosal PGE(2) was higher in the rebamipide groups than in the vehicle-treated group. Rebamipide also suppressed gastric damage induced by HCl in a dose-dependent manner. A COX-2 inhibitor blocked the rebamipide-induced increase in mucosal PGE(2), and mucosal protection induced by rebamipide. The results indicate that rebamipide induces COX-2 expression, increases PGE(2) levels, and enhances gastric mucosal defense in a COX-2-dependent manner. Thus, COX-2 has an important role in the effects of rebamipide on gastric mucosal protection.
近期研究表明，促分裂原诱导型环氧化酶（COX-2）在胃黏膜中有表达。瑞巴派特是一种黏膜保护剂，可增强前列腺素（PG）的合成。本研究旨在阐明瑞巴派特诱导黏膜保护的机制。将雄性Sprague-Dawley大鼠每日给予5、15或50mg/kg的瑞巴派特，持续14天。采用蛋白质印迹分析测定胃黏膜中组成型环氧化酶（COX-1）和COX-2的表达。另一组大鼠用于检测：1）给予和未给予COX-2抑制剂预处理时胃中前列腺素E2（PGE2）的水平；2）瑞巴派特对0.6N盐酸所致胃损伤的保护作用；3）COX-2抑制剂对瑞巴派特诱导的胃黏膜保护作用的影响。瑞巴派特治疗后，大鼠胃黏膜中COX-2表达增强，而COX-1表达无明显变化。瑞巴派特组的胃黏膜PGE2水平高于赋形剂处理组。瑞巴派特还以剂量依赖的方式抑制盐酸诱导的胃损伤。COX-2抑制剂可阻断瑞巴派特诱导的黏膜PGE2增加以及瑞巴派特诱导的黏膜保护作用。结果表明，瑞巴派特以COX-2依赖的方式诱导COX-2表达、增加PGE2水平并增强胃黏膜防御。因此，COX-2在瑞巴派特对胃黏膜保护的作用中起重要作用。
