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雷贝拉唑通过改善小鼠杯状细胞分化缓解放射性结肠炎。

Rebamipide alleviates radiation-induced colitis through improvement of goblet cell differentiation in mice.

机构信息

Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.

Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.

出版信息

J Gastroenterol Hepatol. 2018 Apr;33(4):878-886. doi: 10.1111/jgh.14021. Epub 2018 Jan 19.

DOI:10.1111/jgh.14021
PMID:29047150
Abstract

BACKGROUND AND AIM

Radiation-induced colitis is a common clinical problem associated with radiotherapy and accidental exposure to ionizing radiation. Goblet cells play a pivotal role in the intestinal barrier against pathogenic bacteria. Rebamipide, an anti-gastric ulcer drug, has the effects to promote goblet cell proliferation. The aim of this study was to investigate whether radiation-induced colonic injury could be alleviated by rebamipide.

METHODS

This study orally administered rebamipide for 6 days to mice, which were subjected to 13 Gy abdominal irradiation, to evaluate the therapeutic effects of rebamipide against radiation-induced colitis. To confirm the effects of rebamipide on irradiated colonic epithelial cells, this study used the HT29 cell line.

RESULTS

Rebamipide clearly alleviated the acute radiation-induced colitis, as reflected by the histopathological data, and significantly increased the number of goblet cells. The drug also inhibited intestinal inflammation and protected from bacterial translocation during acute radiation-induced colitis. Furthermore, rebamipide significantly increased mucin 2 expression in both the irradiated mouse colon and human colonic epithelial cells. Additionally, rebamipide accelerated not only the recovery of defective tight junctions but also the differentiation of impaired goblet cells in an irradiated colonic epithelium, which indicates that rebamipide has beneficial effects on the colon.

CONCLUSIONS

Rebamipide is a therapeutic candidate for radiation-induced colitis, owing to its ability to inhibit inflammation and protect the colonic epithelial barrier.

摘要

背景与目的

放射性肠炎是一种与放射治疗和意外接触电离辐射相关的常见临床问题。杯状细胞在肠道屏障抵御致病菌方面发挥着关键作用。瑞巴派特是一种抗胃溃疡药物,具有促进杯状细胞增殖的作用。本研究旨在探讨瑞巴派特是否能减轻放射性结肠炎。

方法

本研究通过口服瑞巴派特 6 天,对接受 13Gy 腹部照射的小鼠进行治疗,以评估瑞巴派特对放射性结肠炎的治疗效果。为了确认瑞巴派特对辐射诱导的结肠上皮细胞的作用,本研究使用 HT29 细胞系。

结果

瑞巴派特明显缓解了急性放射性结肠炎,反映在组织病理学数据上,并显著增加了杯状细胞的数量。该药物还抑制了肠道炎症,并在急性放射性结肠炎期间防止了细菌易位。此外,瑞巴派特显著增加了照射小鼠结肠和人结肠上皮细胞中粘蛋白 2 的表达。此外,瑞巴派特不仅加速了受损紧密连接的恢复,还加速了受损杯状细胞在放射性结肠上皮中的分化,这表明瑞巴派特对结肠有有益的影响。

结论

瑞巴派特是放射性肠炎的治疗候选药物,因为它具有抑制炎症和保护结肠上皮屏障的能力。

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