GLP-2 delays but does not prevent the onset of necrotizing enterocolitis in preterm pigs.
GLP-2 delays but does not prevent the onset of necrotizing enterocolitis in preterm pigs.
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DOI：
10.1097/mpg.0b013e318286891e
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发表时间：
2013-06
影响因子：
2.9
通讯作者：
Burrin DG
中科院分区：
文献类型：
--
作者：
Benight NM;Stoll B;Olutoye OO;Holst JJ;Burrin DG
坏死性小肠结肠炎（NEC）是一种复杂的疾病，被认为是早产儿胃肠道不成熟的结果。全胃肠外营养（TPN）诱导的肠功能障碍可能会增加肠内喂养后NEC的风险。我们假设，先前归因于肠道激素胰高血糖素样肽-2（GLP-2）的肠道营养和抗炎作用与TPN联合给药时，将降低早产仔猪NEC的发生率。早产新生仔猪通过TPN喂养，并连续输注人GLP-2（100 μg · kg−1 ·d −1）或对照生理盐水2天（n = 12/组）。第3天，停止TPN，每3小时给予猪口胃配方饲料，并继续GLP-2或对照治疗，直至出现NEC临床体征，持续96小时，并采集组织用于分子和组织学终点。GLP-2治疗延迟了NEC的发作，但无法预防两组中发生的高NEC发生率（约70%）和严重程度。GLP-2给药猪的组织学损伤较少，近端肠重量和粘膜绒毛高度增加，但隐窝深度或Ki-67阳性细胞未增加。GLP-2处理猪的肠髓过氧化物酶炎症标志物未发生变化，血清淀粉样蛋白A水平较高。GLP-2没有预防NEC和促炎反应，尽管粘膜损伤有所减少，营养作用增加。
Necrotizing enterocolitis (NEC) is complex disease thought to occur as a result of an immaturity of the gastrointestinal tract of preterm infants. Intestinal dysfunction induced by total parental nutrition (TPN) may increase the risk for NEC upon introduction of enteral feeding. We hypothesized that the intestinal trophic and anti-inflammatory actions previously ascribed to the gut hormone, glucagon-like peptide-2 (GLP-2), would reduce the incidence of NEC when given in combination with TPN in preterm piglets. Preterm, newborn piglets were nourished by TPN and infused continuously with either human GLP-2 (100 μg · kg−1 · day−1) or control saline for 2 days (n = 12/group). On day 3, TPN was discontinued and pigs were given orogastric formula feeding every 3 hours, and continued GLP-2 or control treatment until the onset of clinical signs of NEC for an additional 96 hours and tissue was collected for molecular and histological endpoints. GLP-2 treatment delayed the onset of NEC but was unable to prevent a high NEC incidence (~70%) and severity that occurred in both groups. GLP-2–treated pigs had less histological injury and increased proximal intestinal weight and mucosal villus height, but not crypt depth or Ki-67–positive cells. Inflammatory markers of intestinal myeloperoxidase were unchanged and serum amyloid A levels were higher in GLP-2–treated pigs. GLP-2 did not prevent NEC and a proinflammatory response despite some reduction in mucosal injury and increased trophic effect.