MUCOSAL PROTECTIVE FACTORS IN HUMAN MILK

新生儿坏死性小肠结肠炎（NEC）是小肠急性坏死，是新生儿重症监护病房收治的婴儿中最常见的非呼吸性、危及生命的疾病。虽然NEC的病因学和流行病学特征尚不清楚，但与NEC密切相关的两个主要因素是早产和肠内喂养。几组科学家得出的一个惊人的观察结果是，母乳喂养可以降低早产儿患NEC的风险。这种有益的效果没有观察到喂养婴儿配方奶粉。我们最近证明，人乳含有保护因子，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，母乳中至少有两种保护因素，一种是热稳定的，另一种是热敏感的。在初步结果的基础上，我们假设乳源性因子保护肠黏膜屏障功能。我们的长期目标是确定母乳介导的胃肠粘膜保护机制，并确定乳源性粘膜保护因子在预防新生儿胃肠疾病（如NEC）中的作用。我们朝着这个目标的下一步将是分离两种不同的牛奶传播的保护因子，防止过氧化氢引起的屏障破坏，并表征它们的物理和化学性质，以揭示它们的身份。这一目标将通过以下方式实现：1)通过液相色谱分离保护因子以达到均匀性；2)鉴定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特性，并为进一步表征母乳对粘膜保护的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