The protective and anti-inflammatory effects of glucagon-like peptide-2 in an experimental rat model of necrotizing enterocolitis
The protective and anti-inflammatory effects of glucagon-like peptide-2 in an experimental rat model of necrotizing enterocolitis
复制标题
DOI：
10.1016/j.peptides.2015.07.025
复制
发表时间：
2016-01-01
期刊：
影响因子：
3
通讯作者：
Matsufuji, Hiroshi
中科院分区：
文献类型：
--
作者：
Nakame, Kazuhiko;Kaji, Tatsuru;Matsufuji, Hiroshi
坏死性小肠结肠炎 (NEC) 是一种破坏性胃肠道疾病，会影响早产儿。胰高血糖素样肽-2 (GLP-2) 是一种肠营养激素，可减轻炎症。我们怀疑 GLP-2 在 NEC 实验大鼠模型中具有保护和抗炎作用。通过高渗配方肠内喂养、窒息应激和肠内给予脂多糖（LPS）诱导新生大鼠NEC。将大鼠随机分为以下四组：母乳喂养组、NEC组、给予80μg/kg/天GLP-2的NEC+GLP-2(L)组和给予800μg/kg/天GLP-2的NEC+GLP-2(H)组。 GLP-2 在应激前每 6 小时皮下注射一次。所有存活超过 96 小时或出现痛苦迹象的动物均被安乐死。 NEC+GLP-2(H)组的临床疾病评分显着低于NEC组。 NEC+GLP-2(H)组的NEC评分和生存率较NEC和NEC+GLP-2(L)组显着改善。与NEC组相比，GLP-2治疗组的绒毛高度和隐窝深度均显着增加。各组间隐窝细胞增殖指数无显着差异。回肠间质TNF-α。 NEC+GLP-2(H)组的IL-6水平降低至与母畜喂养组相同的水平。高剂量 GLP-2 给药可提高 NEC 的发生率和生存率。它还减少了粘膜炎症细胞因子的产生。这些结果支持 GLP-2 在 NEC 治疗中的潜在治疗作用。 (C) 2015 Elsevier Inc. 保留所有权利。
Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease, that affects premature infants. Glucagon-like peptide-2 (GLP-2) is an intestinotrophic hormone and reduces the inflammation. We suspected that GLP-2 would have protective and anti-inflammatory effects in an experimental rat model of NEC. NEC was induced in newborn rats by enteral feeding with hyperosmolar formula, asphyxial stress and enteral administration of lipopolysaccharide (LPS). Rats were randomly divided into the following four groups: dam-fed, NEC, NEC + GLP-2(L) given 80 mu g/kg/day of GLP-2, and NEC + GLP-2(H) given 800 mu g/kg/day of GLP-2. GLP-2 was administered subcutaneously every 6 h before stress. All animals surviving beyond 96 h or any that developed signs of distress were euthanized. The clinical sickness score in the NEC + GLP-2(H) group was significantly lower than that in the NEC group. The NEC score and the survival rate in the NEC + GLP-2(H) group was significantly improved compared with those in the NEC and the NEC + GLP-2(L) groups. Villous height and crypt depth in both the GLP-2 treatment groups were significantly increased compared with those in the NEC group. There were no significant differences in the crypt cell proliferation indices among the groups. Ileal interstitial TNF-alpha. and IL-6 level in the NEC + GLP-2(H) group was decreased to the same levels in the dam-fed group. High dose GLP-2 administration improved the incidence and survival rate for NEC. It also decreased mucosal inflammatory cytokine production. These results support a potential therapeutic role for GLP-2 in the treatment of NEC. (C) 2015 Elsevier Inc. All rights reserved.