Mathur P P, Smyth R D
J Pharmacol Exp Ther. 1980 Feb;212(2):333-6.
The relation between the incidence of gastric ulceration, basal acid output and serum gastrin concentration was studied in the pyloric-ligated normal rat and the rat with established adjuvant disease (polyarthritis). Although there was no significant difference in either gastric secretions or basal acid output, serum gastrin was significantly higher in the adjuvant rat than in the normal rat, independent of the nutritional state of the animal. The incidence of the gastric lesions was eight times greater in adjuvant rats compared to controls in a 6-hour pyloric-ligation period. When the period of pyloric ligation was increased from 6 to 17 hr, there was 91% increase in gastric lesions in polyarthritic rats. Histopathology of the lesions in the polyarthritic rat showed diffuse and focal submucosal edema with polymorphonuclear inflammatory cell infiltration in the submucosa of the fundic and antral areas of the stomach. The increased susceptibility of the polyarthritic rat to gastric ulceration could be related to a combination of experimental stress and hypergastrinemia. Since similar elevations in serum gastrin have been reported in the rheumatoid arthritis in man, it is herein proposed that the polyarthritic rat could be used as a screening model for the evaluation of the ulcerogenicity potential of nonsteroidal anti-inflammatory drugs.
在幽门结扎的正常大鼠和已患佐剂病(多关节炎)的大鼠中,研究了胃溃疡发生率、基础胃酸分泌量和血清胃泌素浓度之间的关系。尽管在胃分泌物或基础胃酸分泌量方面没有显著差异,但佐剂大鼠的血清胃泌素水平显著高于正常大鼠,且与动物的营养状态无关。在6小时的幽门结扎期内,佐剂大鼠的胃部病变发生率比对照组高8倍。当幽门结扎时间从6小时增加到17小时时,患多关节炎的大鼠胃部病变增加了91%。多关节炎大鼠病变的组织病理学表现为胃底和胃窦部黏膜下弥漫性和局灶性水肿,黏膜下层有多形核炎性细胞浸润。多关节炎大鼠对胃溃疡易感性增加可能与实验性应激和高胃泌素血症共同作用有关。由于在人类类风湿性关节炎中也有类似的血清胃泌素升高情况,因此本文提出,多关节炎大鼠可作为一种筛选模型,用于评估非甾体抗炎药的致溃疡潜力。