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肿瘤坏死因子α抗体对大鼠实验性坏死性小肠结肠炎的保护作用。

Protective effect of tumor necrosis factor alpha antibody on experimental necrotizing enterocolitis in the rat.

作者信息

Seitz Guido, Warmann Steven W, Guglielmetti Andres, Heitmann Heike, Ruck Peter, Kreis Martin E, Fuchs Jörg

机构信息

Department of Pediatric Surgery, University Children's Hospital, 72076 Tübingen, Germany.

出版信息

J Pediatr Surg. 2005 Sep;40(9):1440-5. doi: 10.1016/j.jpedsurg.2005.05.043.

DOI:10.1016/j.jpedsurg.2005.05.043
PMID:16150346
Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSION

Tumor necrosis factor alpha antibody may have an attenuating effect on experimental NEC in rats.

摘要

背景

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。

方法

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。

结果

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)。

结论

肿瘤坏死因子α抗体可能对大鼠实验性NEC有减轻作用。

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