Biesterveld Ben E, Koehler Shannon M, Heinzerling Nathan P, Rentea Rebecca M, Fredrich Katherine, Welak Scott R, Gourlay David M
Medical College of Wisconsin, Milwaukee, Wisconsin.
Division of Pediatric Surgery, Department of Surgery, Children's Hospital of Wisconsin, Milwaukee, Wisconsin.
J Surg Res. 2015 Jun 15;196(2):235-40. doi: 10.1016/j.jss.2015.02.030. Epub 2015 Feb 19.
Intestinal alkaline phosphatase (IAP) activity is decreased in necrotizing enterocolitis (NEC), and IAP supplementation prevents NEC development. It is not known if IAP given after NEC onset can reverse the course of the disease. We hypothesized that enteral IAP given after NEC induction would not reverse intestinal injury.
NEC was induced in Sprague-Dawley pups by delivery preterm followed by formula feedings with lipopolysaccharide (LPS) and hypoxia exposure and continued up to 4 d. IAP was added to feeds on day 2 until being sacrificed on day 4. NEC severity was scored based on hematoxylin and eosin-stained terminal ileum sections, and AP activity was measured using a colorimetric assay. IAP and interleukin-6 expression were measured using real time polymerase chain reaction.
NEC pups' alkaline phosphatase (AP) activity was decreased to 0.18 U/mg compared with controls of 0.57 U/mg (P < 0.01). Discontinuation of LPS and hypoxia after 2 d increased AP activity to 0.36 U/mg (P < 0.01). IAP supplementation in matched groups did not impact total AP activity or expression. Discontinuing LPS and hypoxia after NEC onset improved intestinal injury scores to 1.14 compared with continued stressors, score 2.25 (P < 0.01). IAP supplementation decreased interleukin-6 expression two-fold (P < 0.05), though did not reverse NEC intestinal damage (P = 0.5).
This is the first work to demonstrate that removing the source of NEC improves intestinal damage and increases AP activity. When used as a rescue treatment, IAP decreased intestinal inflammation though did not impact injury making it likely that IAP is best used preventatively to those neonates at risk.
坏死性小肠结肠炎（NEC）患者的肠道碱性磷酸酶（IAP）活性降低，补充IAP可预防NEC的发生。目前尚不清楚NEC发病后给予IAP是否能逆转疾病进程。我们推测，NEC诱导后给予肠内IAP不会逆转肠道损伤。
通过早产，随后用脂多糖（LPS）进行配方奶喂养并暴露于低氧环境，诱导斯普拉格-道利幼崽发生NEC，并持续4天。在第2天向饲料中添加IAP，直至第4天处死。根据苏木精和伊红染色的回肠末端切片对NEC严重程度进行评分，并使用比色法测量碱性磷酸酶（AP）活性。使用实时聚合酶链反应测量IAP和白细胞介素-6的表达。
与对照组的0.57 U/mg相比，NEC幼崽的碱性磷酸酶（AP）活性降至0.18 U/mg（P < 0.01）。2天后停止LPS和低氧暴露可使AP活性增加至0.36 U/mg（P < 0.01）。匹配组中补充IAP对总AP活性或表达没有影响。与持续应激因素组（评分2.25）相比，NEC发病后停止LPS和低氧暴露可使肠道损伤评分改善至1.14（P < 0.01）。补充IAP可使白细胞介素-6表达降低两倍（P < 0.05），但并未逆转NEC肠道损伤（P = 0.5）。
这是第一项证明去除NEC来源可改善肠道损伤并增加AP活性的研究。当用作挽救治疗时，IAP可减轻肠道炎症，但不影响损伤，这表明IAP最好预防性地用于有风险的新生儿。
