Arai H, Mizuo M, Marubuchi S, Nakagawa M, Mori Y
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Nihon Yakurigaku Zasshi. 1998 Aug;112(2):117-24. doi: 10.1254/fpj.112.117.
The effect of T-593, a novel antiulcer agent, was investigated with respect to gastric bleeding and lesions induced by indomethacin (3 mg/kg, s.c.) and water (23 degrees C) immersion stress (IM-WIS) with perfusion of HCl (0.13N) into the rat stomach. It was found that the total amounts of gastric bleeding and lesions after IM-WIS with perfusion of HCl were more significantly decreased in T-593 (1 mg/kg, i.v., 0.1 mg/kg/hr, d.i.)- and secretion (15 CU/kg/hr, d.i.)-treated rats, respectively. On the other hand, famotidine (1 mg/kg, i.v.) did not affect gastric bleeding and lesions. The gastric mucosal blood flow (GMBF) reduction was induced by IM-WIS. T-593 (0.03-0.1 mg/kg/hr, d.i.) inhibited the GMBF reduction dose-dependently. The GMBF improvement by T-593 disappeared with pretreatment of L-NAME (2 mg/kg, s.c.) and was recovered by L-arginine (50 mg/kg, i.v.). This indicates that GMBF improvement by T-593 is dependent on EDRF (NO). This interesting property of T-593 is expected to contribute to the clinical promotion of ulcer healing.
研究了新型抗溃疡药物T - 593对吲哚美辛（3毫克/千克，皮下注射）和水（23摄氏度）浸浴应激（IM - WIS）诱导的胃出血及损伤的影响，同时向大鼠胃内灌注0.13N盐酸。结果发现，在接受T - 593（1毫克/千克，静脉注射，0.1毫克/千克/小时，持续输注）和分泌素（15 CU/千克/小时，持续输注）治疗的大鼠中，IM - WIS并灌注盐酸后胃出血和损伤的总量分别显著降低。另一方面，法莫替丁（1毫克/千克，静脉注射）对胃出血和损伤没有影响。IM - WIS可导致胃黏膜血流量（GMBF）降低。T - 593（0.03 - 0.1毫克/千克/小时，持续输注）剂量依赖性地抑制GMBF降低。T - 593对GMBF的改善作用在预先给予L - NAME（2毫克/千克，皮下注射）后消失，而L - 精氨酸（50毫克/千克，静脉注射）可使其恢复。这表明T - 593对GMBF的改善作用依赖于内皮舒张因子（NO）。T - 593的这一有趣特性有望促进溃疡愈合的临床应用。
