Higashimura Yasuki, Naito Yuji, Takagi Tomohisa, Tanimura Yuko, Mizushima Katsura, Harusato Akihito, Fukui Akifumi, Yoriki Hiroyuki, Handa Osamu, Ohnogi Hiromu, Yoshikawa Toshikazu
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan; Department of Food Factor Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
J Gastroenterol Hepatol. 2014 Feb;29(2):310-7. doi: 10.1111/jgh.12373.
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.
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.
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.
Results suggest that oral administration of AGOs prevents NSAID-induced intestinal injury.
非甾体抗炎药（NSAIDs）在临床医学中常用，但会导致胃肠道糜烂、溃疡和出血。目前尚未确立预防和治疗NSAIDs所致小肠损伤的有效药物。本研究探讨琼脂寡糖（AGOs）对NSAIDs诱导的小鼠小肠损伤的影响。
用非甾体抗炎药吲哚美辛处理小鼠以诱导肠道损伤。比较给予AGOs的小鼠和对照小鼠的黏膜损伤程度。采用定量实时聚合酶链反应（qRT-PCR）、蛋白质印迹法和免疫组织化学法检测血红素加氧酶-1（HO-1）的表达。采用qRT-PCR和酶联免疫吸附测定法检测角质形成细胞趋化因子（KC）的表达。
给予AGOs可诱导小鼠小肠黏膜中HO-1表达。诱导主要在F4/80阳性巨噬细胞中观察到。给予AGOs可抑制吲哚美辛所致溃疡评分增加、髓过氧化物酶活性增加和KC表达增加。相反，HO抑制剂可消除AGOs介导的肠道损伤预防作用。在小鼠腹腔巨噬细胞中，AGOs增强HO-1表达并抑制脂多糖诱导的KC表达。此外，AGOs增强了替代性活化巨噬细胞标志物精氨酸酶-1、甘露糖受体-1和几丁质酶3样蛋白3的表达。
结果表明口服AGOs可预防NSAIDs诱导的肠道损伤。
