Department of Women's and Children's Health, Uppsala University, Dag Hammarskjölds Väg 14B, 752 37, Uppsala, Sweden.
Department of Pediatric Surgery, University Children's Hospital, Uppsala, Sweden.
BMC Pediatr. 2022 Nov 5;22(1):640. doi: 10.1186/s12887-022-03681-9.
Necrotizing enterocolitis (NEC) is an inflammatory bowel disease in preterm neonates with high morbidity and mortality. The only treatment available is supportive with broad-spectrum antibiotics and gastrointestinal rest. Better understanding of the pathogenesis is crucial for the development of new therapies. Vascular adhesion protein-1 (VAP-1), expressed in human blood vessels and lymphatic, plays a crucial role in the pathogenesis of inflammatory diseases in adults. The aim of the study was to investigate the VAP-1 expression in the intestines of infants affected by NEC.
Intestinal tissues from 42 preterm infants with NEC were examined with immunohistochemical staining using antibodies against VAP-1 and semi-automated digital image analysis was performed to determine tissue protein expression of VAP-1 in blood vessels located in the submucosa. Intestinal tissue from 26 neonates that underwent laparotomy and ileostomy due to other intestinal surgical conditions served as controls. Clinical data and protein expression were compared between the NEC-group and Controls.
Mean gestational age was lower in NEC infants compared to controls, 26.6 ± 3.0 gestational weeks versus 36.5 ± 4.0 (p < 0.001) but without any significant difference in median postnatal age at surgery; for NEC 8 (5-27) days and for controls 3 (1-36) days (p = 0.6). Low VAP-1 correlated with increased risk for developing NEC in the logistic regression (p < 0.001). Multiple linear regression showed that both gestational age and NEC were independent predictors of VAP-1 expression.
VAP-1 may play a role in the pathogenesis of NEC. Diminished expression of VAP-1 independent of maturation could indicate arrested vascular development in infants suffering from NEC. Further studies are needed to elucidate the role of VAP-1 in NEC.
坏死性小肠结肠炎(NEC)是一种早产儿炎症性肠病,具有较高的发病率和死亡率。目前唯一可用的治疗方法是支持治疗,包括广谱抗生素和胃肠休息。更好地了解发病机制对于开发新疗法至关重要。血管黏附蛋白-1(VAP-1)在人类血管和淋巴管中表达,在成人炎症性疾病的发病机制中起着至关重要的作用。本研究旨在研究 VAP-1 在患 NEC 的婴儿肠道中的表达。
使用针对 VAP-1 的抗体对 42 名患有 NEC 的早产儿的肠道组织进行免疫组织化学染色,并进行半自动数字图像分析,以确定位于黏膜下层的血管中 VAP-1 的组织蛋白表达。26 名因其他肠道手术条件而行剖腹术和肠造口术的新生儿的肠道组织作为对照。比较 NEC 组和对照组的临床数据和蛋白表达。
与对照组相比,NEC 婴儿的平均胎龄较低,为 26.6±3.0 周,而中位数的出生后手术年龄无显著差异;NEC 组为 8(5-27)天,对照组为 3(1-36)天(p=0.6)。逻辑回归显示,VAP-1 低表达与 NEC 发生的风险增加相关(p<0.001)。多元线性回归显示,胎龄和 NEC 均是 VAP-1 表达的独立预测因子。
VAP-1 可能在 NEC 的发病机制中起作用。VAP-1 的表达减少与成熟无关,这可能表明患有 NEC 的婴儿的血管发育停滞。需要进一步的研究来阐明 VAP-1 在 NEC 中的作用。