Isani Mubina, Illingworth Laura, Herman Eliot, Schmidt Monica, Barron Lauren, Bowling Jordan, Elizee Melissa, Bai Iris, Gayer Christopher, Grishin Anatoly, Erwin Christopher R, Ford Henri R, Warner Brad W
Division of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, CA.
University of Arizona School of Plant Sciences, Tucson, AZ.
J Pediatr Surg. 2018 Jun;53(6):1203-1207. doi: 10.1016/j.jpedsurg.2018.02.084. Epub 2018 Mar 8.
Epidermal Growth Factor (EGF) reduces necrotizing enterocolitis (NEC). However, its high cost virtually prohibits clinical use. To reduce cost, soybean expressing human EGF was developed. Here we report effectiveness of soybean-derived EGF in experimental NEC.
Newborn rats were subjected to the NEC-inducing regimen of formula feeding and hypoxia. Formula was supplemented with extract from EGF-expressing or empty soybeans. NEC pathology was determined microscopically. Localization of tight junction proteins JAM-A and ZO-1 was examined by immunofluorescence and levels of mucosal COX-2 and iNOS mRNAs by real time PCR.
Soybean extract amounts corresponding to 150μg/kg/day EGF caused considerable mortality, whereas those corresponding to 75μg/kg/day EGF were well tolerated. There was no significant difference in NEC scores between animals fed plain formula and formula supplemented with empty soybean extract. Soybean-EGF-supplemented formula at 75μg/kg/day EGF significantly decreased NEC, attenuated dissociation of JAM-A and ZO-1 proteins from tight junctions, and reduced intestinal expression of COX-2 and iNOS mRNAs.
Supplementation with soybean-expressed EGF significantly decreased NEC in the rat model. Soybean-expressed EGF may provide an economical solution for EGF administration and prophylaxis of clinical NEC.
表皮生长因子(EGF)可降低坏死性小肠结肠炎(NEC)的发生率。然而,其高昂的成本几乎使其无法应用于临床。为降低成本,人们开发了能表达人EGF的大豆。在此,我们报告大豆源性EGF在实验性NEC中的有效性。
对新生大鼠采用配方奶喂养和低氧的NEC诱导方案。配方奶中添加了表达EGF的大豆提取物或空载体大豆提取物。通过显微镜检查NEC病理情况。采用免疫荧光法检测紧密连接蛋白JAM-A和ZO-1的定位,并用实时PCR检测黏膜COX-2和iNOS mRNA的水平。
相当于150μg/kg/天EGF的大豆提取物剂量导致相当高的死亡率,而相当于75μg/kg/天EGF的剂量则耐受性良好。喂食普通配方奶的动物与喂食添加空载体大豆提取物配方奶的动物在NEC评分上无显著差异。添加75μg/kg/天EGF的大豆-EGF配方奶显著降低了NEC的发生率,减轻了JAM-A和ZO-1蛋白与紧密连接的解离,并降低了肠道COX-2和iNOS mRNA的表达。
在大鼠模型中,添加大豆表达的EGF可显著降低NEC的发生率。大豆表达的EGF可能为EGF给药及临床NEC的预防提供一种经济的解决方案。