Nonsteroidal anti-inflammatory drug-induced visible and invisible small intestinal injury
Nonsteroidal anti-inflammatory drug-induced visible and invisible small intestinal injury
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DOI：
10.3164/jcbn.12-116
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发表时间：
2013-07-01
影响因子：
2.4
通讯作者：
Kasugai, Kunio
中科院分区：
文献类型：
--
作者：
Ito, Yoshitsugi;Sasaki, Makoto;Kasugai, Kunio
小肠粘膜的渗透是诱发肠病的关键机制。我们研究了瑞巴派特在健康受试者中的作用，这些受试者患有双氯芬酸诱导的小肠损伤和通透性。在这项交叉研究中，每个治疗期为1周，洗脱期为4周。给予双氯芬酸（75 mg/天）和奥美拉唑（20 mg/天）加瑞巴派特（300 mg/天）或安慰剂。在每个阶段的第1天和第7天进行胶囊内镜检查和糖渗透性试验。入组了10例健康受试者。第7天，两组10例受试者中有6例观察到小肠损伤。在第一个治疗期，安慰剂组乳果糖的尿液排泄量从初始剂量的0.30%增加到0.50%，瑞巴派特组从0.13%增加到0.33%。尽管小肠粘膜损伤恢复，但两组的渗透性增加导致乳果糖持续高水平（安慰剂组为0.50%至1.06%，瑞巴派特组为0.33%至1.12%），持续4周洗脱期。双氯芬酸给药诱导肠病和小肠通透性过高。洗脱期持续的高渗透性可能表明存在不可见的脆弱性。
Permeation of the small intestinal mucosa is a key mechanism in the induction of enteropathy. We investigated the effect of rebamipide in healthy subjects with diclofenac-induced small intestinal damage and permeability. In this crossover study, each treatment period was 1 week with a 4-week washout period. Diclofenac (75 mg/day) and omeprazole (20 mg/day) plus rebamipide (300 mg/day) or placebo were administered. Capsule endoscopy and a sugar permeability test were performed on days 1 and 7 in each period. Ten healthy subjects were enrolled. Small intestinal injuries were observed on day 7 in 6 of 10 subjects in both groups. Urinary excretion of administered lactulose increased from 0.30% to 0.50% of the initial dose during the first treatment period in the placebo group, and from 0.13% to 0.33% in the rebamipide group. Despite recovery from small-intestinal mucosal damage, the increased permeability in both groups resulted in sustained high levels of lactulose (0.50% to 1.06% in the placebo group and 0.33% to 1.12% in the rebamipide group) through the 4-week washout period. Diclofenac administration induced enteropathy and hyperpermeability of the small intestine. The sustained hyperpermeability during the washout period may indicate the presence of invisible fragility.