Yokel R A, Dickey K M
College of Pharmacy, University of Kentucky, Lexington.
Gastroenterology. 1991 May;100(5 Pt 1):1201-5.
A method producing persistent gastric ulcers in the rhesus monkey by combined mucosal injury and gamma-irradiation was modified and evaluated in the rabbit. gamma-Irradiation (800-1000 cGy) immediately after removal of 2-mm-diameter sections of antral mucosa resulted in ulcer craters 5-7 days later. Ulcer sites were characterized by loss of the mucosa, muscularis mucosa, and much of the submucosa. The exposed submucosa was coated with fibrin and necrotic debris infiltrated with heterophils, the rabbit equivalent of neutrophils. These ulcers strongly resemble human chronic gastric ulcers. Binding of Carafate (sucralfate; Marion Laboratories, Inc., Kansas City, MO) and Maalox (magnesia-alumina oral suspension; Wm. H. Rorer, Inc., Ft. Washington, PA) to ulcer and nearby nonulcer sites in the antrum was assessed 1 hour after drug dosing. Drug binding was determined by aluminum quantitation of stomach wall punch biopsies at necropsy. Both drugs significantly increased aluminum bound to the stomach wall compared with vehicle treatment. Significantly more antiulcer drug was bound to ulcer sites than to nearby nonulcer sites only after sucralfate administration. This model of persistent gastric ulcer should be useful to further study gastric ulcer pathogenesis and treatment.
一种通过联合黏膜损伤和γ射线照射在恒河猴身上产生持续性胃溃疡的方法在兔子身上进行了改良和评估。在切除直径2毫米的胃窦黏膜切片后立即进行γ射线照射（800 - 1000 cGy），5 - 7天后会形成溃疡坑。溃疡部位的特征是黏膜、黏膜肌层和大部分黏膜下层缺失。暴露的黏膜下层覆盖有纤维蛋白和坏死碎片，其中浸润有嗜异性粒细胞，相当于兔子的中性粒细胞。这些溃疡与人类慢性胃溃疡非常相似。在给药1小时后，评估了胃溃宁（硫糖铝；马里恩实验室公司，密苏里州堪萨斯城）和氢氧化铝镁混悬液（威廉·H·罗勒公司，宾夕法尼亚州华盛顿堡）与胃窦溃疡部位及附近非溃疡部位的结合情况。通过尸检时对胃壁穿孔活检组织进行铝定量来确定药物结合情况。与赋形剂处理相比，两种药物均显著增加了与胃壁结合的铝含量。仅在给予硫糖铝后，与溃疡部位结合的抗溃疡药物明显多于附近非溃疡部位。这种持续性胃溃疡模型对于进一步研究胃溃疡的发病机制和治疗应该是有用的。
