Chokshi Nikunj K, Guner Yigit S, Hunter Catherine J, Upperman Jeffrey S, Grishin Anatoly, Ford Henri R
Department of Pediatric Surgery, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA.
Semin Perinatol. 2008 Apr;32(2):92-9. doi: 10.1053/j.semperi.2008.01.002.
Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal disease encountered in the premature infant. Although the inciting events leading to NEC remain elusive, various risk factors, including prematurity, hypoxemia, formula feeding, and intestinal ischemia, have been implicated in the pathogenesis of NEC. Data from our laboratory and others suggest that NEC evolves from disruption of the intestinal epithelial barrier, as a result of a combination of local and systemic insults. We postulate that nitric oxide (NO), an important second messenger and inflammatory mediator, plays a key role in intestinal barrier failure seen in NEC. Nitric oxide and its reactive nitrogen derivative, peroxynitrite, may affect gut barrier permeability by inducing enterocyte apoptosis (programmed cell death) and necrosis, or by altering tight junctions or gap junctions that normally play a key role in maintaining epithelial monolayer integrity. Intrinsic mechanisms that serve to restore monolayer integrity following epithelial injury include enterocyte proliferation, epithelial restitution via enterocyte migration, and re-establishment of cell contacts. This review focuses on the biology of NO and the mechanisms by which it promotes epithelial injury while concurrently disrupting the intrinsic repair mechanisms.
坏死性小肠结肠炎（NEC）是早产儿中最常见的危及生命的胃肠道疾病。尽管导致NEC的诱发事件仍不明确，但包括早产、低氧血症、配方奶喂养和肠道缺血在内的多种风险因素已被认为与NEC的发病机制有关。我们实验室及其他机构的数据表明，由于局部和全身损伤的共同作用，NEC是由肠上皮屏障破坏演变而来的。我们推测，一氧化氮（NO）作为一种重要的第二信使和炎症介质，在NEC中出现的肠屏障功能障碍中起关键作用。一氧化氮及其活性氮衍生物过氧亚硝酸盐可能通过诱导肠上皮细胞凋亡（程序性细胞死亡）和坏死，或通过改变在维持上皮单层完整性中起关键作用的紧密连接或缝隙连接，来影响肠道屏障通透性。上皮损伤后用于恢复单层完整性的内在机制包括肠上皮细胞增殖、通过肠上皮细胞迁移实现上皮修复以及重新建立细胞接触。本综述重点关注NO的生物学特性及其促进上皮损伤同时破坏内在修复机制的机制。
