Lugo Brian, Ford Henri R, Grishin Anatoly
Department of Surgery, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
J Pediatr Surg. 2007 Jul;42(7):1165-71. doi: 10.1016/j.jpedsurg.2007.02.006.
Necrotizing enterocolitis (NEC) is the most common surgical emergency in premature infants. The underlying etiology of NEC remains unknown, although bacterial colonization of the gut, formula feeding, and perinatal stress have been implicated as putative risk factors. The disease is characterized by exuberant gut inflammation leading to ischemia and coagulation necrosis of the intestinal epithelium. The molecular and cellular mechanisms responsible for these pathologic changes are poorly understood. It has been shown that various exogenous and endogenous mediators such as lipopolysaccharide, inflammatory cytokines, platelet activating factor, and nitric oxide may play a role in the pathogenesis of NEC. Recent studies in our laboratory and others have established a link between NEC and activation of cyclooxygenase-2, the enzyme that catalyzes the rate-limiting step in the biosynthesis of prostanoids. The challenge is in defining the molecular signaling pathways leading to accumulation of these mediators early in the disease progression, before the onset of tissue necrosis and systemic sepsis. Identification and characterization of these pathways could lead to the development of novel treatment strategies to alleviate the morbidity and mortality associated with NEC.
坏死性小肠结肠炎（NEC）是早产儿最常见的外科急症。尽管肠道细菌定植、配方奶喂养和围产期应激被认为是可能的危险因素，但NEC的潜在病因仍不清楚。该疾病的特征是肠道炎症过度，导致肠上皮缺血和凝固性坏死。导致这些病理变化的分子和细胞机制尚不清楚。研究表明，各种外源性和内源性介质，如脂多糖、炎性细胞因子、血小板活化因子和一氧化氮，可能在NEC的发病机制中起作用。我们实验室和其他机构最近的研究已经确立了NEC与环氧合酶-2激活之间的联系，环氧合酶-2是催化前列腺素生物合成限速步骤的酶。挑战在于确定在疾病进展早期、在组织坏死和全身脓毒症发作之前导致这些介质积累的分子信号通路。识别和表征这些通路可能会导致开发新的治疗策略，以减轻与NEC相关的发病率和死亡率。
