Department of Surgery Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
J Surg Res. 2012 Oct;177(2):228-34. doi: 10.1016/j.jss.2012.05.039. Epub 2012 Jun 1.
Supplementation of intestinal alkaline phosphatase (IAP), an endogenous protein expressed in the intestines, decreases the severity of necrotizing enterocolitis (NEC)-associated intestinal injury and permeability. We hypothesized that IAP administration is protective in a dose-dependent manner of the inflammatory response in a neonatal rat model.
Pre- and full-term newborn Sprague-Dawley rat pups were sacrificed on day of life 3. Control pups were vaginally delivered and dam fed. Preterm pups were delivered via cesarean section and exposed to intermittent hypoxia and formula feeds containing lipopolysaccharide (NEC) with and without IAP. Three different standardized doses were administered to a group of pups treated with 40, 4, and 0.4U/kg of bovine IAP (NEC+IAP40, IAP4, or IAP0.4U). Reverse transcription-real-time polymerase chain reaction (RT-PCR) for inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α on liver and lung tissues and serum cytokine analysis for interleukin (IL)-1β, IL-6, IL-10, and TNF-α were performed. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests, expressed as mean±standard error of the mean and P≤0.05 considered significant.
Levels of cytokines IL-1β, IL-6, and TNF-α increased significantly in NEC versus control, returning to control levels with increasing doses of supplemental enteral IAP. Hepatic and pulmonary TNF-α and iNOS messenger ribonucleic acid expressions increased in NEC, and the remaining elevated despite IAP supplementation.
Proinflammatory cytokine expression is increased systemically with intestinal NEC injury. Administration of IAP significantly reduces systemic proinflammatory cytokine expression in a dose-dependent manner. Early supplemental enteral IAP may reduce NEC-related injury and be useful for reducing effects caused by a proinflammatory cascade.
肠道碱性磷酸酶（IAP）是一种在内肠中表达的内源性蛋白质，补充这种酶可以降低坏死性小肠结肠炎（NEC）相关肠损伤和通透性的严重程度。我们假设 IAP 的给药以剂量依赖的方式对新生大鼠模型中的炎症反应具有保护作用。
在出生当天（第 3 天）处死早产和足月的斯普拉格-道利大鼠幼崽。对照组幼崽经阴道分娩并由母鼠喂养。早产儿通过剖宫产分娩，并暴露于间歇性缺氧和含有脂多糖的配方奶中（NEC），并添加或不添加 IAP。一组接受 40、4 和 0.4U/kg 牛 IAP 治疗的幼崽（NEC+IAP40、IAP4 或 IAP0.4U）接受了三种不同的标准化剂量。对肝和肺组织的诱导型一氧化氮合酶（iNOS）和肿瘤坏死因子（TNF）-α进行逆转录实时聚合酶链反应（RT-PCR），并对血清细胞因子进行白细胞介素（IL）-1β、IL-6、IL-10 和 TNF-α分析。数据通过 Kruskal-Wallis 和 Mann-Whitney 检验进行分析，以平均值±标准误表示，P≤0.05 被认为具有统计学意义。
与对照组相比，NEC 组的细胞因子 IL-1β、IL-6 和 TNF-α水平显著升高，随着补充肠内 IAP 的剂量增加而恢复到对照水平。NEC 时肝和肺 TNF-α和 iNOS 信使核糖核酸表达增加，尽管补充了 IAP，但仍保持升高。
肠道 NEC 损伤时全身促炎细胞因子表达增加。IAP 的给药以剂量依赖的方式显著降低全身促炎细胞因子表达。早期补充肠内 IAP 可能减轻 NEC 相关损伤，并有助于减轻促炎级联反应造成的影响。
