Bukhave K, Rask-Madsen J, Hogan D L, Koss M A, Isenberg J I
Department of Biochemistry and Nutrition, Technical University of Denmark.
Gastroenterology. 1990 Oct;99(4):951-5. doi: 10.1016/0016-5085(90)90612-5.
Proximal duodenal mucosal bicarbonate production is impaired in patients with duodenal ulcer disease. Because prostaglandins of the E class increase human proximal duodenal bicarbonate secretion, this study tested the hypothesis that endogenous prostaglandin E2 production is defective in patients with duodenal ulcer. Ten patients, five with active and five with inactive duodenal ulcer disease, were studied along with 10 normal volunteers. The proximal 4 cm of duodenum, the bulb, was isolated and continuously perfused with 154 mmol/L NaCl. Basal bicarbonate secretion was measured for 30 minutes. The test segment was then acidified with a physiological amount of HCl (2 mmol over 5 minutes), and acid-stimulated bicarbonate secretion was measured by pH/PCO2 and back-titration for 55 more minutes. Prostaglandin E2 was measured in the effluents by a radioimmunologic assay validated by gas chromatography-mass spectrometry. Compared with the normal subjects after luminal acidification, the duodenal ulcer patients had significantly greater PGE2 release and decreased total 1-hour bicarbonate output. The peak 5-minute acid-stimulated bicarbonate responses were not significantly different between the duodenal ulcer patients and normal subjects. After luminal acidification, PGE2 output remained elevated in the duodenal ulcer patients but returned promptly to basal in the normal subjects. Furthermore, the ratio of bicarbonate secreted to the amount of PGE2 released was significantly less in the ulcer patients. These findings suggest that patients with duodenal ulcer disease have an impaired mucosal bicarbonate response to endogenous PGE2. The increased acid-stimulated PGE2 response in duodenal ulcer patients suggests a compensatory phenomenon in response to the diminished mucosal bicarbonate production.
十二指肠溃疡病患者近端十二指肠黏膜碳酸氢盐生成受损。由于E类前列腺素可增加人近端十二指肠碳酸氢盐分泌，本研究检验了十二指肠溃疡患者内源性前列腺素E2生成存在缺陷这一假说。对10例患者（5例活动性十二指肠溃疡患者和5例非活动性十二指肠溃疡患者）以及10名正常志愿者进行了研究。分离出十二指肠近端4厘米（球部），并用154 mmol/L氯化钠持续灌注。测量30分钟的基础碳酸氢盐分泌量。然后用生理量的盐酸（5分钟内2 mmol）使测试段酸化，并通过pH/PCO2和反滴定法再测量55分钟的酸刺激碳酸氢盐分泌量。通过气相色谱-质谱法验证的放射免疫分析法测量流出液中的前列腺素E2。与管腔酸化后的正常受试者相比，十二指肠溃疡患者的PGE2释放量显著更高，而1小时总碳酸氢盐输出量降低。十二指肠溃疡患者和正常受试者之间5分钟酸刺激碳酸氢盐反应峰值无显著差异。管腔酸化后，十二指肠溃疡患者的PGE2输出量仍升高，而正常受试者则迅速恢复至基础水平。此外，溃疡患者分泌的碳酸氢盐与释放的PGE2量之比显著更低。这些发现表明，十二指肠溃疡病患者黏膜对内源性PGE2的碳酸氢盐反应受损。十二指肠溃疡患者酸刺激PGE2反应增加表明是对黏膜碳酸氢盐生成减少的一种代偿现象。
