Protective effect of prostaglandin E2 in the gastrointestinal tract during indomethacin treatment of rheumatic diseases
Protective effect of prostaglandin E2 in the gastrointestinal tract during indomethacin treatment of rheumatic diseases
复制标题
吲哚美辛治疗风湿性疾病时前列腺素E2对胃肠道的保护作用
DOI：
10.1016/0016-5085(80)90859-8
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发表时间：
1980
期刊：
影响因子：
29.4
通讯作者：
S. Bergström
中科院分区：
文献类型：
--
作者：
C. Johansson;B. Kollberg;R. Nordemar;K. Samuelson;S. Bergström
非甾体类抗炎药（NSAID）会导致实验动物胃和肠出血性溃疡的形成。通过预先局部施用前列腺素可以预防这种损伤，这表明前列腺素对胃肠粘膜具有保护作用。通过测量吲哚美辛治疗 18 名风湿性疾病患者期间的粪便失血量，研究了人类的保护作用，同时口服补充或不口服补充 1 mg 前列腺素 E2，每天 3 次。该研究采用随机双盲交叉设计，使用 51Cr 标记的红细胞作为胃肠道出血的标记物。吲哚美辛使每日粪便失血量从 1.0 ± 0.3 毫升增加至 2.8 ± 0.6 毫升（P < 0.005）。当同时服用口服 PGE2 时，失血量减少至每天 1.1 ± 0.2 ml（P < 0.01），即降至对照水平。前列腺素E2的副作用可以忽略不计，吲哚美辛对关节状态和症状的有益作用也没有受到干扰。在重复的血液测试中没有记录到任何变化，除了在吲哚美辛治疗期间血红蛋白略有降低和血清钙有小幅但具有统计学意义的降低外，迄今为止在血钙正常的人类受试者中尚未描述过这种效应。本研究在人体中也证实了口服前列腺素 E2 对胃肠粘膜的保护作用。这种保护作用与胃酸分泌无关，口服前列腺素E2不会抑制胃酸分泌。这一发现可能具有临床应用价值，因为胃肠道副作用和出血是风湿性疾病患者停用非甾体抗炎药的常见原因。
Nonsteroidal antiinflammatory drugs (NSAID) induce the formation of bleeding gastric and intestinal ulcers in experimental animals. The damage can be prevented by prior local administration of prostaglandins, indicating that prostaglandins have protective properties on the gastrointestinal mucosa. The protective effect was studied in humans by measuring the fecal blood loss during indomethacin treatment of 18 patients with rheumatic diseases with and without concomitant oral supplementation with 1 mg prostaglandin E2three times daily. The study had a randomized double-blind crossover design using51Cr-labeled erythrocytes as marker of gastrointestinal bleeding. Indomethacin increased the daily fecal blood loss from 1.0 ± 0.3 to 2.8 ± 0.6 ml (P < 0.005). When oral PGE2was taken concomitantly, the blood loss was reduced to 1.1 ± 0.2 ml daily (P < 0.01), i.e., to the control level. Side effects of prostaglandin E2were negligible, and the beneficial effect of indomethacin on joint status and symptoms was not interfered with. No changes were recorded in repeated blood tests except for a slightly reduced hemoglobin and a small but statistically significant reduction of serum-calcium during indomethacin treatment, an effect hitherto not described in normocalcemic human subjects. A protective effect on the gastrointestinal mucosa by oral prostaglandin E2has by the present study been demonstrated also in humans. The protection is unrelated to the gastric acid secretion, which is not inhibited by oral prostaglandin E2. The finding may have clinical application, as gastrointestinal side effects and bleeding are common reasons for discontinuation of NSAID in patients with rheumatic diseases.