MUCOSAL PROTECTIVE FACTORS IN HUMAN MILK

新生儿坏死性小肠结肠炎（NEC）是小肠的急性坏死，是新生儿重症监护病房中最常见的非呼吸道、危及生命的疾病。虽然NEC的病因学和流行病学特征知之甚少，但与NEC密切相关的两个主要因素是早产和肠内喂养。几组科学家的一个惊人的观察是，母乳喂养降低了早产儿NEC的风险。通过喂养婴儿配方奶粉未观察到这种有益效果。我们最近证明，人乳中含有保护因子，可保护肠上皮屏障功能免受氧化应激诱导的破坏。我们的初步研究表明，人乳中至少有两种保护因子，一种是热稳定的，另一种是热敏感的。初步结果的基础上，它是假设，乳源性因素保护肠粘膜屏障功能。我们的长期目标是确定参与母乳介导的胃肠道粘膜保护的机制，并确定乳源性粘膜保护因子在预防新生儿胃肠道疾病（如NEC）中的作用。我们实现这一目标的下一步将是分离两种不同的乳源性保护因子，以防止过氧化氢诱导的屏障破坏，并表征其物理和化学性质，以揭示其身份。这一目标将通过以下方式实现：1）通过液相色谱法将保护因子分离至均一性，以及2）表征分离的保护因子的物理和化学性质。这些研究将揭示母乳中至少两种不同的粘膜保护因子的身份，并为进一步表征母乳粘膜保护机制及其在预防新生儿胃肠道疾病中的作用提供基础

Neonatal necrotizing enterocolitis (NEC), the acute necrosis of the small intestine, is the most common non-respiratory, life-threatening disease among infants admitted to neonatal intensive care units. Although etiologic and epidemiologic characteristics of NEC are poorly understood, two major factors closely associated with NEC are prematurity and enteral feeding. A striking observation made by several groups of scientists is that feeding breast milk reduces the risk of NEC in premature infants. Such a beneficial effect was not observed by feeding infant formula. We recently demonstrated that human milk contains protective factors that protect the intestinal epithelial barrier function from oxidative-stress induced disruption. Our preliminary studies indicate that there are at least two protective factors in human milk, one heat stable and the other heat-sensitive. On the basis of preliminary results it is hypothesized that milk-borne factors protect the intestinal mucosal barrier function. Our long-range goal is to determine the mechanism involved in breast milk-mediated protection of the gastrointestinal mucosa, and to determine the role of milk-borne mucosal protective factors in preventing neonatal gastrointestinal diseases, such as NEC. Our next step towards this goal will be to isolate two distinct milk-borne protective factors that prevent hydrogen peroxide-induced barrier disruption, and to characterize their physical and chemical properties to reveal their identity. This goal will be achieved by: 1) isolation of protective factors to homogeneity by liquid chromatography, and 2) characterization of physical and chemical properties of isolated protective factors. These studies will reveal the identity of at least two distinct mucosal protective factors in breast milk, and provide the basis for further characterization of the mechanisms involved in mucosal protection by breast milk, and their role in preventing neonatal gastrointestinal diseases