Preventive effect of agaro-oligosaccharides on non-steroidal anti-inflammatory drug-induced small intestinal injury in mice
Preventive effect of agaro-oligosaccharides on non-steroidal anti-inflammatory drug-induced small intestinal injury in mice
复制标题
DOI：
10.1111/jgh.12373
复制
发表时间：
2014-02-01
影响因子：
4.1
通讯作者：
Yoshikawa, Toshikazu
中科院分区：
文献类型：
--
作者：
Higashimura, Yasuki;Naito, Yuji;Yoshikawa, Toshikazu
背景和目的：非类固醇抗炎药(NSAIDs)是临床上常用的药物，可引起胃肠道的侵蚀、溃疡和出血。目前还没有建立起预防和治疗非类固醇抗炎药所致小肠损伤的有效药物。本研究旨在探讨琼脂低聚糖(AGOS)对非甾体类抗炎药(NSAID)诱导的小鼠小肠损伤的影响。比较注射AGO的小鼠和对照组小鼠的粘膜损伤程度。用实时定量聚合酶链式反应(qRT-PCR)、Western blotting和免疫组织化学方法检测HO-1的表达。用定量逆转录聚合酶链式反应和酶联免疫吸附试验检测角质形成细胞趋化因子(KC)的表达。结果：AGO可诱导小鼠小肠粘膜HO-1的表达。诱导主要见于F4/80阳性巨噬细胞。AGO可抑制吲哚美辛引起的溃疡评分、髓过氧化物酶活性和KC表达的增加。相反，HO抑制剂取消了AGO介导的预防肠道损伤的作用。在小鼠腹腔巨噬细胞中，AGOS促进HO-1的表达，并抑制内毒素诱导的KC的表达。此外，AGOS还可促进交替激活的巨噬细胞标志物精氨酸酶-1、甘露糖受体-1和几丁质酶-3的表达。结论：口服AGOS可预防NSAID所致的肠道损伤。
Background and Aim: Non-steroidal anti-inflammatory drugs (NSAIDs), which are commonly used in clinical medicine, cause erosion, ulcers, and bleeding in the gastrointestinal tract. No effective agent for the prevention and treatment of small intestinal injury by NSAIDs has been established. This study investigates the effects of agaro-oligosaccharides (AGOs) on NSAID-induced small intestinal injury in mice.Methods: Mice were treated with indomethacin, an NSAID, to induce intestinal injury. The respective degrees of mucosal injury of mice that received AGO and control mice were compared. Heme oxygenase-1 (HO-1) expression using quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry were measured. The expression of keratinocyte chemoattractant (KC) was measured using qRT-PCR and enzyme-linked immunosorbent assay.Results: AGO administration induced HO-1 expression in mouse small intestinal mucosa. Induction was observed mainly in F4/80 positive macrophages. The increased ulcers score, myeloperoxidase activity, and KC expression by indomethacin were inhibited by AGO administration. Conversely, HO inhibitor cancelled AGO-mediated prevention of intestinal injury. In mouse peritoneal macrophages, AGOs enhanced HO-1 expression and suppressed lipopolysaccharide-induced KC expression. Furthermore, AGOs enhanced the expressions of alternatively activated macrophage markers arginase-1, mannose receptor-1, and chitinase 3-like 3.Conclusions: Results suggest that oral administration of AGOs prevents NSAID-induced intestinal injury.