Feng Jiexiong, El-Assal Osama N, Besner Gail E
Department of Surgery, Children's Hospital, and Ohio State University College of Medicine and Public Health, Columbus, OH 43205, USA.
J Pediatr Surg. 2006 Jan;41(1):144-9; discussion 144-9. doi: 10.1016/j.jpedsurg.2005.10.018.
We have previously demonstrated that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent intestinal cytoprotective agent. The aim of this study was to determine the effect of enterally administered HB-EGF on the incidence of necrotizing enterocolitis (NEC) in neonatal rats.
Necrotizing enterocolitis was induced in neonatal rats delivered by C-section on day 21 of gestation by exposure to repeated cycles of hypoxia and hypothermia plus administration of hypertonic formula feeding (HHHTF) plus enteral administration of lipopolysaccharide (LPS) (2 mg/kg). Neonatal rats were randomly assigned to breast-feeding, hypertonic formula feeding, HHHTF + LPS, and HHHTF + LPS with HB-EGF (600 mug/kg) supplementation in the formula. Animals were monitored until 96 hours of life and assessed for death, histological NEC, and intestinal mucosal permeability.
The incidence of NEC in the HHHTF group was higher than that in the breast-feeding or hypertonic formula feeding groups. With administration of HB-EGF, the incidence and severity of NEC were significantly decreased. Administration of HB-EGF also increased rat pup survival rate and extended survival time. In addition, treatment with HB-EGF significantly decreased intestinal permeability to fluorescein isothiocyanate-dextran.
We conclude that HB-EGF reduces the incidence and severity of NEC in a neonatal rat model, with simultaneous preservation of gut barrier integrity. These results support our contention that HB-EGF administration may represent a useful therapeutic and prophylactic therapy for the treatment of NEC.
我们之前已经证明，肝素结合表皮生长因子样生长因子（HB-EGF）是一种有效的肠道细胞保护剂。本研究的目的是确定经肠道给予HB-EGF对新生大鼠坏死性小肠结肠炎（NEC）发病率的影响。
在妊娠第21天通过剖宫产分娩的新生大鼠中，通过反复暴露于缺氧和低温循环、给予高渗配方奶喂养（HHHTF）以及经肠道给予脂多糖（LPS，2 mg/kg）来诱导坏死性小肠结肠炎。新生大鼠被随机分为母乳喂养组、高渗配方奶喂养组、HHHTF + LPS组以及在配方奶中补充HB-EGF（600 μg/kg）的HHHTF + LPS组。对动物进行监测直至出生后96小时，并评估其死亡情况、组织学NEC以及肠道黏膜通透性。
HHHTF组的NEC发病率高于母乳喂养组或高渗配方奶喂养组。给予HB-EGF后，NEC的发病率和严重程度均显著降低。给予HB-EGF还提高了幼鼠的存活率并延长了存活时间。此外，HB-EGF治疗显著降低了肠道对异硫氰酸荧光素 - 葡聚糖的通透性。
我们得出结论，HB-EGF可降低新生大鼠模型中NEC的发病率和严重程度，同时保持肠道屏障的完整性。这些结果支持我们的观点，即给予HB-EGF可能是治疗NEC的一种有用的治疗和预防方法。
