Increased Gap Density Predicts Weakness of the Epithelial Barrier In Vivo by Confocal Laser Endomicroscopy in Indomethacin-Induced Enteropathy
Increased Gap Density Predicts Weakness of the Epithelial Barrier In Vivo by Confocal Laser Endomicroscopy in Indomethacin-Induced Enteropathy
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DOI：
10.1007/s10620-014-3076-8
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发表时间：
2014-02
影响因子：
3.1
通讯作者：
Shaokui Shi;Han Wang;Hui Gao;Zhen Li;Fei-xue Chen;X. Zuo;Yan-Qing Li
中科院分区：
文献类型：
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作者：
Shaokui Shi;Han Wang;Hui Gao;Zhen Li;Fei-xue Chen;X. Zuo;Yan-Qing Li
背景与目的肠上皮屏障在非甾体抗炎药所致肠病的发病机制中起重要作用，其破坏常与细胞脱落增加有关。本研究旨在通过共聚焦激光显微内镜（CLE）观察吲哚美辛诱导的大鼠小肠粘膜损伤的差距密度变化，并探讨其机制及黏膜保护剂如何改善肠上皮屏障功能障碍。CLE有望为评价非甾体抗炎药引起的人类肠病和评估药物efficacy. MethodsUse CLE的新技术，我们建立了一种方法来评估，在真实的时间，肠道损伤后，给药吲哚美辛在Wistar大鼠小肠差距密度调查。粘膜保护剂替普瑞酮和抑酸剂雷贝拉唑，然后通过灌胃给药前和给药后的吲哚美辛，和影响肠上皮屏障的机制investigated.ResultsUsing CLE，间隙可以清楚地观察到，很容易区分杯状细胞。吲哚美辛给药后间隙密度增加。在此过程中，肿瘤坏死因子-α、核因子-κB、caspase-3表达上调，紧密连接表达下调，导致上皮屏障受损。结论CLE能客观、准确、真实的及时地检测缝隙密度。替普瑞酮和雷贝拉唑可通过干预肿瘤坏死因子-α通路预防吲哚美辛诱导的肠道病变，保护上皮屏障。缝隙密度有望成为评价肠道炎症和药物疗效的指标。
Background and AimsThe intestinal epithelial barrier plays an important role in the pathogenesis of non-steroidal anti-inflammatory drug-induced enteropathy, and its disruption is often associated with increased cell shedding. The purpose of this report is to observe the gap density in indomethacin-induced small intestinal damage by confocal laser endomicroscopy (CLE) and to investigate the mechanisms involved in this process and how mucosal protectants improve intestinal epithelial barrier dysfunction. CLE is expected to provide a new way for evaluating non-steroidal anti-inflammatory drugs-induced enteropathy in humans and assessing drug efficacy.MethodsUsing the new technique of CLE, we established a method to evaluate, in real time, intestinal damage after the administration of indomethacin in Wistar rats by investigating the gap density in the small intestine. The mucosal protectant teprenone and acid-suppressant rabeprazole were then given by gavage before and after the administration of indomethacin, and the mechanisms affecting the intestinal epithelial barrier were investigated.ResultsUsing CLE, gaps could be clearly observed and easily distinguished from goblet cells. Gap density was increased after the administration of indomethacin. During this process, the expression of tumor necrosis factor-α, nuclear factor-κB, and caspase-3 was up-regulated and the expression of tight junctions was down-regulated, which led to the damage of the epithelial barrier. Teprenone and rabeprazole could intervene in this pathway and protect the integrity of the epithelial barrier.ConclusionsCLE can be objective, accurate, and real time in investigating gap density. Teprenone and rabeprazole can prevent indomethacin-induced intestinal lesions and protect the epithelial barrier by intervening in the tumor necrosis factor-α pathway. Gap density was expected to be an indicator of evaluating intestinal inflammation and drug efficacy.