Kurebayashi Y, Asano M, Hashizume T, Akashi A
Arch Int Pharmacodyn Ther. 1984 Sep;271(1):155-68.
Dulcerozine-induced duodenal ulcers in rats were studied in order to establish the optimum conditions for a routine production of ulcers and to elucidate their possible pathogenesis. Single doses of dulcerozine administered either subcutaneously or orally produced a dose-related duodenal ulceration in rats. The ulcerogenic effect of dulcerozine was most potent when given subcutaneously to 24-hr fasted animals at 300 mg/kg. At this dose, deep or perforating ulcers were consistently produced within 18 hr, but mortality due to general toxicity of the agent was excluded at least up to 48 hr. Feeding of animals resulted in a significant reduction in susceptibility to dulcerozine. An antacid and antisecretory agents prevented dulcerozine-induced duodenal ulceration in a dose-dependent manner. Either pylorus ligation or vagotomy completely inhibited duodenal ulceration in response to dulcerozine. In addition, an ulcerogenic dose (300 mg/kg s.c.) of dulcerozine evoked a sustained gastric hypersecretion in pylorus ligated rats. These results suggest that a stimulating action on gastric secretion may be, at least in part, responsible for the ulcerogenic property of dulcerozine. The present study provides a new reliable model for investigations of the pathogenesis and therapy of duodenal ulcer disease.
为了确定大鼠十二指肠溃疡常规造模的最佳条件并阐明其可能的发病机制，对双氯嗪诱导的大鼠十二指肠溃疡进行了研究。皮下或口服单剂量双氯嗪可在大鼠中产生剂量相关的十二指肠溃疡。当以300mg/kg的剂量皮下给予禁食24小时的动物时，双氯嗪的致溃疡作用最为显著。在此剂量下，18小时内持续产生深度或穿孔性溃疡，但至少在48小时内排除了因该药物的全身毒性导致的死亡。给动物喂食会显著降低其对双氯嗪的易感性。抗酸剂和抗分泌剂以剂量依赖的方式预防双氯嗪诱导的十二指肠溃疡。幽门结扎或迷走神经切断术均可完全抑制双氯嗪引起的十二指肠溃疡。此外，致溃疡剂量（300mg/kg皮下注射）的双氯嗪可引起幽门结扎大鼠持续的胃酸高分泌。这些结果表明，对胃分泌的刺激作用可能至少部分地导致了双氯嗪的致溃疡特性。本研究为十二指肠溃疡病的发病机制和治疗研究提供了一种新的可靠模型。
