Seitz Guido, Warmann Steven W, Guglielmetti Andres, Heitmann Heike, Ruck Peter, Kreis Martin E, Fuchs Jörg
Department of Pediatric Surgery, University Children's Hospital, 72076 Tübingen, Germany.
J Pediatr Surg. 2005 Sep;40(9):1440-5. doi: 10.1016/j.jpedsurg.2005.05.043.
Necrotizing enterocolitis (NEC) is a common and devastating disorder of premature infants. Elevated proinflammatory cytokines, especially tumor necrosis factor alpha (TNF-alpha), have been implicated in the pathogenesis of NEC. The aim of this study was to evaluate the effects of TNF-alpha on the inflammatory response in NEC by immunoneutralizing TNF-alpha with a selective antibody.
Neonatal Sprague-Dawley rats were divided in 3 groups: group 1 (n = 20), a NEC-like enterocolitis was induced by formula feeding, asphyxia, and cold exposure; group 2 (n = 9), animals were treated like in group 1 and additionally received TNF-alpha antibody intraperitoneally; and group 3 (n = 17), animals were dam-fed (controls). Animals were killed in case of imminent death or after 96 hours. Specimens from small bowel were processed for blinded histologic (H&E) and immunhistologic (myeloperoxidase [MPO]) analysis.
In group 1, animals developed severe NEC (mean NEC score, 3.28 +/- 0.32; mean MPO, 65.85 +/- 9.46). In group 2, animals developed mild NEC (mean NEC score, 1.72 +/- 0.41; mean MPO, 34.33 +/- 9.69; P < .05). In group 3, no NEC was induced (mean NEC score, 0.0 +/- 0; mean MPO, 6 +/- 1.32; P < .05).
Tumor necrosis factor alpha antibody may have an attenuating effect on experimental NEC in rats.
坏死性小肠结肠炎(NEC)是早产儿常见且严重的疾病。促炎细胞因子升高,尤其是肿瘤坏死因子α(TNF-α),与NEC的发病机制有关。本研究旨在通过用选择性抗体免疫中和TNF-α来评估其对NEC炎症反应的影响。
将新生Sprague-Dawley大鼠分为3组:第1组(n = 20),通过配方奶喂养、窒息和冷暴露诱导类似NEC的小肠结肠炎;第2组(n = 9),动物的处理方式与第1组相同,并额外腹腔注射TNF-α抗体;第3组(n = 17),动物由母鼠哺乳(对照组)。动物在濒死时或96小时后处死。取小肠标本进行盲法组织学(苏木精-伊红染色[H&E])和免疫组织学(髓过氧化物酶[MPO])分析。
第1组动物发生严重NEC(平均NEC评分,3.28±0.32;平均MPO,65.85±9.46)。第2组动物发生轻度NEC(平均NEC评分,1.72±0.41;平均MPO,34.33±9.69;P <.05)。第3组未诱导出NEC(平均NEC评分,0.0±0;平均MPO,6±1.32;P <.05)。
肿瘤坏死因子α抗体可能对大鼠实验性NEC有减轻作用。