Heparin-binding EGF-like growth factor (HB-EGF) and necrotizing enterocolitis.
Heparin-binding EGF-like growth factor (HB-EGF) and necrotizing enterocolitis.
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DOI：
10.1053/j.sempedsurg.2005.05.005
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发表时间：
2005-08-01
影响因子：
1.7
通讯作者：
Besner, Gail E
中科院分区：
文献类型：
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作者：
Feng, Jiexiong;El-Assal, Osama N;Besner, Gail E
坏死性小肠结肠炎（NEC）是一种常见的和毁灭性的胃肠道疾病，主要发生在早产儿。尽管在治疗方面取得了各种进步，但这种疾病的死亡率仍然很高。在过去的十年中，我们实验室的研究表明，肝素结合的表皮生长因子样生长因子（HB-EGF）是表皮生长因子（EGF）家族的一员，可以在体外保护肠上皮细胞（IEC）免受各种形式的损伤。此外，我们使用成年大鼠肠道I/R损伤模型和NEC新生大鼠幼鼠模型来证明HB-EGF可以保护肠道免受损伤。在新生大鼠模型中给药HB-EGF后，NEC的发生率从65%降低到27.3% (P < 0.05)，组织学损伤评分从2降低到1.1 （P < 0.05）。存活率由25%提高到63.6%，生存时间由59小时延长到73小时（P < 0.05）。此外，通过使用新生儿肠切除术治疗NEC的人体标本，我们发现在切除边缘的正常肠道区域，内源性HB-EGF mRNA的表达高于急性NEC的肠道。内源性HB-EGF可能参与损伤恢复过程中上皮细胞的修复、增殖和再生。外源性给药HB-EGF促进肠道损伤的体外和体内恢复。综上所述，这些结果支持HB-EGF在未来治疗NEC中的潜在治疗作用。
Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal disease that occurs predominantly in premature infants. Despite various advances in management, the mortality of this disease remains high. During the last decade, studies from our laboratory have shown that heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family, can protect intestinal epithelial cells (IEC) from various forms of injury in vitro. Furthermore, we have used both an intestinal I/R injury model in adult rats, and a neonatal rat pup model of NEC, to show that HB-EGF can protect the intestines from injury. On administration of HB-EGF in the neonatal rat model, the incidence of NEC is reduced from 65% to 27.3% (P < 0.05), and the histological injury score is decreased from 2 to 1.1 (P < 0.05). In addition, the survival rate is increased from 25% to 63.6% and the survival time extended from 59 hours to 73 hours (P < 0.05). In addition, using human specimens from newborns undergoing bowel resection for NEC, we found that the expression of endogenous HB-EGF mRNA in normal areas of the intestine at the resection margins was higher than that of the intestine afflicted with acute NEC. Endogenous HB-EGF may be involved in epithelial cell repair, proliferation, and regeneration during recovery from injury. Exogenous administration of HB-EGF potentiates recovery from intestinal injury in vitro and in vivo. Taken together, these results support a potential therapeutic role for HB-EGF in the treatment of NEC in the future.