PATHOGENESIS OF NEONATAL NECROTIZING ENTEROCOLITIS

描述（改编自研究者的摘要和/或目的）： 第一个奖项的总体目标是测试 假设细菌定植和粘附的模式 肠在决定新生儿是否发生NEC中起作用。 的 拟议的工作是下列意见的延伸， 申请人：1）地方性NEC不能归因于单一的 感染原; 2）大肠杆菌（Escherichia coli，E. 大肠杆菌）菌株分离自 NEC病例和对照显示出高度的依从性 体外和体内肠上皮也引起细胞损伤， 3)由这些细菌引起的粘附和细胞损伤被阻断 通过与来自对照组的选定肠球菌菌株共感染 而NEC病例的肠球菌则无此作用。 在这 应用，研究提出，以确定什么机制是 负责遵守E.大肠杆菌试验菌株至肠道 上皮细胞抗E.杆菌作为 以及该菌株的非粘附性等基因突变体将用于 定义允许细菌粘附的粘附分子， 肠道细胞及不同环境因素的影响 与NEC的细菌粘附相关。 另一系列实验 将试图确定来自对照组婴儿的肠球菌如何阻断 E.大肠杆菌转化为肠上皮细胞。 的第三个组成部分 本项目将重点研究宿主对细菌-上皮细胞 粘附，特别注意肿瘤坏死的变化 因子（TNF）。最后，研究将 以确定是否有抗炎剂， 超氧化物歧化酶（SOD）、米索前列醇和地塞米松可减弱 由附着的细菌引起的组织坏死。

DESCRIPTION (adapted from investigator's abstract and/or aims): The overall objective of this FIRST award application is to test the hypothesis that patterns of bacterial colonization and adherence in the bowel play a role in determining whether newborns develop NEC. The proposed work represents an extension of the following observations by the applicant: 1) endemic NEC cannot be attributed to a single infectious agent, 2) Escherichia coli (E. coli) strains isolated from NEC cases and controls that exhibit a high degree of adherence to intestinal epithelia in-vitro and in-vivo also cause cell injury, and 3) the adherence and cell injury elicited by these bacteria are blocked by co-infection with selected strains of Enterococci from control infants while Enterococci from NEC cases had no such effect. In this application, studies are proposed to determine what mechanisms are responsible for the adherence of the E. coli test strain to intestinal epithelia. Antisera directed against specific adhesions on E. coli as well as non-adherent isogeneic mutants of the strain will be used to define the adhesion molecule that allows for bacterial adherence to intestinal cells and the influence of different environmental factors relevant to NEC on bacterial adherence. Another series of experiments will attempt to determine how Enterococci from control infants block the adherence of E. coli to intestinal epithelia. The third component of this project will focus on host responses to bacteria-epithelial cell adhesion, with particular attention devoted to changes in tumor necrosis factor (TNF) elicited by adherent bacteria. Finally, studies will be performed to determine whether anti-inflammatory agents such as superoxide dismutase (SOD), misoprostol, and dexamethasone attenuate the tissue necrosis caused by adherent bacteria.