Freston J W
University of Connecticut Health Center, Farmington 06032.
Toxicol Pathol. 1988;16(2):260-6. doi: 10.1177/019262338801600219.
Both genetic and nongenetic factors predispose to ulcer diathesis. At the mucosal level ulcers result from an imbalance between aggressive factors and mucosal defense. Ulcer therapy reduces aggressive forces, bolsters defense, or both. Gastric acid, the major aggressive factor, may have its secretion inhibited or it may be partially neutralized by antacids. H2 receptor antagonists competitively block histamine occupancy of H2 receptors on parietal cells, thereby preventing stimulation of adenylate cyclase, cAMP rises, and activation of protein kinase and H+/K+ATPase. Prostaglandins inhibit acid secretion largely by preventing histamine-induced cAMP rises. Proton pump inhibitors bind H+/K+ATPase. Antimuscarinics inhibit acetylcholine receptors on the parietal cell, thereby blocking Ca2+ entry and subsequent activation of protein kinase and the proton pump. Mucosal defense is enhanced by certain prostaglandins, colloidal bismuth subcitrate and sucralfate. Prostaglandins stimulate secretion of bicarbonate and mucus, among other effects. Colloidal bismuth and sucralfate bind to proteins in the ulcer base and stimulate bicarbonate and mucus secretion, partially, in the case of sucralfate, by increasing endogenous prostanoid synthesis. Sucralfate also binds pepsin and bile acids. Colloidal bismuth temporarily eradicates mucosal colonization by Campylobacter pylori, another putative agent in ulcer diathesis.
遗传因素和非遗传因素均易导致溃疡素质。在黏膜层面，溃疡是由攻击因素与黏膜防御之间的失衡所致。溃疡治疗可降低攻击力量、增强防御或二者兼顾。胃酸是主要的攻击因素，其分泌可被抑制，或可被抗酸剂部分中和。H2受体拮抗剂竞争性阻断组胺对壁细胞上H2受体的占据，从而防止腺苷酸环化酶的刺激、cAMP升高以及蛋白激酶和H⁺/K⁺ATP酶的激活。前列腺素主要通过防止组胺诱导的cAMP升高来抑制胃酸分泌。质子泵抑制剂与H⁺/K⁺ATP酶结合。抗胆碱能药物抑制壁细胞上的乙酰胆碱受体，从而阻断Ca²⁺进入以及随后蛋白激酶和质子泵的激活。某些前列腺素、枸橼酸铋钾和硫糖铝可增强黏膜防御。前列腺素除其他作用外，还刺激碳酸氢盐和黏液的分泌。胶体铋和硫糖铝与溃疡底部的蛋白质结合，并刺激碳酸氢盐和黏液分泌，就硫糖铝而言，部分是通过增加内源性前列腺素的合成来实现的。硫糖铝还结合胃蛋白酶和胆汁酸。胶体铋可暂时根除幽门螺杆菌在黏膜的定植，幽门螺杆菌是溃疡素质中的另一种假定致病因素。
