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Glucagon-like peptide-2 and common therapeutics in a murine model of ulcerative colitis

机译:胰高血糖素样肽2和溃疡性结肠炎的小鼠模型中的常见治疗方法

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The intestinal hormone glucagon-like peptide-2 (GLP-2) enhances bowel growth and reduces the severity of colonic injury in dextran sulfate sodium (DSS)-induced colitis in mice. In humans, ulcerative colitis is normally treated with aminosalicylates (ASAs) and corticosteroids (CSs) to reduce inflammaton. However, whether the intestinotropic efects of GLP-2 are altered when combined with ASAs and/or CSs has not previously been explored. Thus, each agent [vehicle, ASA (sulfasalazine), CS (methylprednisolone), and ASA + CS] was administered alone or with GLP-2 to normal mice or mice with 3.5% DSS in the drinking water, for 10 consecutive days. GLP-2 treatment of DSS-mice increased survival and small intestinal weight (p < 0.05), and decreased body weight loss and colonic damage (p < 0.05). Furthermore, weight loss and colonic damage (p < 0.05). Furthermore, GLP-2 increased the number of proliferating cells in the colonic crypts of DSS-mice (p < 0.05). Administration of ASA, CS, or ASA + CS alone did not affect growth of the intestine in DSS-mice. However, administration of GLP-2 in combination with ASA was permissive for the beneficial effects of GLP-2 on survival and colonic damage, whereas CS treatment prevented these effects of GLP-2. Concomitant administration of GLP-2 with ASA + CS resulted in intermediate effects. No differences between colonic myeloperoxidase activity or IkappaB levels (an inhibitor of the nuclear factor-kappaB pro-inflammatory pathway) were found for any of these therapeutic agents. When taken together, the ability of GLP-2 to protect colonic mucosal architecture in DSS-colitis, and its effectiveness when given in combination with ASA, but not with CS, suggests a novel approach for the treatment of patients with colitis.
机译:肠道激素胰高血糖素样肽2(GLP-2)可增强肠道生长,并降低硫酸葡聚糖硫酸钠(DSS)诱导的结肠炎中结肠损伤的严重性。在人类中,溃疡性结肠炎通常用氨基水杨酸酯(ASAs)和皮质类固醇(CSs)治疗,以减少炎症。但是,以前尚未探讨过与ASA和/或CSs结合使用时GLP-2的肠溶作用是否会改变。因此,将每种试剂[车辆,ASA(柳氮磺胺吡啶),CS(甲基泼尼松龙)和ASA + CS]单独或与GLP-2一起给予正常小鼠或饮用水中含3.5%DSS的小鼠,连续10天。 GLP-2治疗DSS小鼠可增加存活率和小肠重量(p <0.05),并减少体重减轻和结肠损伤(p <0.05)。此外,体重减轻和结肠损伤(p <0.05)。此外,GLP-2增加了DSS小鼠结肠隐窝中增殖细胞的数量(p <0.05)。单独施用ASA,CS或ASA + CS不会影响DSS小鼠肠道的生长。但是,将GLP-2与ASA联合使用对于GLP-2对生存和结肠损伤的有益作用是允许的,而CS治疗则阻止了GLP-2的这些作用。将GLP-2与ASA + CS并用会产生中间作用。对于这些治疗剂中的任何一种,未发现结肠髓过氧化物酶活性或IkappaB水平(核因子-kappaB促炎途径的抑制剂)之间的差异。综上所述,GLP-2在DSS结肠炎中保护结肠粘膜结构的能力以及与ASA(而非CS)联合使用时的有效性,提出了一种治疗结肠炎患者的新方法。

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