Ischemia and necrotizing enterocolitis: where, when, and how.
Ischemia and necrotizing enterocolitis: where, when, and how.
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DOI：
10.1053/j.sempedsurg.2005.05.003
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发表时间：
2005-08-01
影响因子：
1.7
通讯作者：
Nowicki, Philip T
中科院分区：
文献类型：
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作者：
Nowicki, Philip T
虽然人们普遍认为缺血会导致坏死性小肠结肠炎 (NEC) 的发病机制，但关于这一作用仍存在三个重要问题。首先，血管病理生理学发生在肠道循环的哪个部位？该事件很可能始于壁内微循环，特别是刺穿肠壁的小动脉和粘膜下小动脉丛，因为它们代表了肠道中阻力调节的主要部位。粘膜损伤还可能破坏下游绒毛小动脉的完整性或功能，导致其损伤；此后，有害刺激可能通过下游小静脉和淋巴管上升到粘膜下血管。第二，在发病过程中何时发生缺血？缺血不太可能是 NEC 的唯一引发因素；相反，缺血更有可能是由其他事件引发的，例如粘膜表面的炎症。在这种情况下，缺血很可能在疾病扩展中发挥次要但关键的作用。第三，缺血是如何发生的？新生儿肠道内血管阻力的调节主要取决于血管收缩肽内皮素-1 (ET-1) 的内皮生成和血管舒张剂自由基一氧化氮 (NO) 的内皮生成之间的平衡。在正常情况下，这种平衡非常有利于 NO 诱导的血管舒张，从而导致低静息阻力和高流速。然而，破坏内皮细胞功能的因素，例如缺血再灌注、持续低流量灌注或促炎介质，会改变 ET-1:NO 平衡，有利于收缩。此后独特的 ET-1-NO 相互作用可能会促进这种收缩的快速延伸，产生粘性级联，其中缺血迅速延伸到肠道的较大部分。
While it is accepted that ischemia contributes to the pathogenesis of necrotizing enterocolitis (NEC), three important questions regarding this role subsist. First, where within the intestinal circulation does the vascular pathophysiology occur? It is most likely that this event begins within the intramural microcirculation, particularly the small arteries that pierce the gut wall and the submucosal arteriolar plexus insofar as these represent the principal sites of resistance regulation in the gut. Mucosal damage might also disrupt the integrity or function of downstream villous arterioles leading to damage thereto; thereafter, noxious stimuli might ascend into the submucosal vessels via downstream venules and lymphatics. Second, when during the course of pathogenesis does ischemia occur? Ischemia is unlikely to the sole initiating factor of NEC; instead, it is more likely that ischemia is triggered by other events, such as inflammation at the mucosal surface. In this context, it is likely that ischemia plays a secondary, albeit critical role in disease extension. Third, how does the ischemia occur? Regulation of vascular resistance within newborn intestine is principally determined by a balance between the endothelial production of the vasoconstrictor peptide endothelin-1 (ET-1) and endothelial production of the vasodilator free radical nitric oxide (NO). Under normal conditions, the balance heavily favors NO-induced vasodilation, leading to a low resting resistance and high rate of flow. However, factors that disrupt endothelial cell function, eg, ischemia-reperfusion, sustained low-flow perfusion, or proinflammatory mediators, alter the ET-1:NO balance in favor of constriction. The unique ET-1-NO interaction thereafter might facilitate rapid extension of this constriction, generating a viscous cascade wherein ischemia rapidly extends into larger portions of the intestine.