Neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts.
Neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts.
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DOI：
10.1007/s10024-002-0602-z
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发表时间：
2003-01
期刊：
影响因子：
--
通讯作者：
Gonzalez-Crussi F
中科院分区：
文献类型：
--
作者：
Hsueh W;Caplan MS;Qu XW;Tan XD;De Plaen IG;Gonzalez-Crussi F
坏死性小肠结肠炎（NEC）是一种主要影响早产儿的疾病，是新生儿重症监护病房发病率和死亡率的主要原因。虽然已经确定了几个诱发因素，如早产，肠道喂养和感染，其发病机制仍然是难以捉摸的。在过去的20年里，我们建立了多种大鼠NEC动物模型，发现了多种内源性介质，尤其是血小板活化因子（PAF），可能在NEC中发挥关键作用。在成年大鼠中，注射PAF可诱导肠坏死，PAF拮抗剂可预防细菌内毒素、缺氧或肿瘤坏死因子-a（TNF-α）加内毒素引起的肠损伤。新生动物缺氧和肠道喂养引起的病变也是如此。NEC患者血浆PAF-乙酰水解酶（降解PAF的酶）水平升高，血浆PAF-乙酰水解酶水平降低。在我们的NEC实验模型中的初始事件可能是多形核白细胞（PMN）活化和粘附到肠中的小静脉，其启动涉及促炎介质（包括TNF、补体、白介素和白三烯C4）的局部炎症反应。随后的去甲肾上腺素释放和肠系膜血管收缩导致内脏缺血和再灌注。细菌产物（例如，内毒素）在局部粘膜屏障破坏期间进入肠组织，并且内毒素与PAF协同作用以放大炎症。由活化的白细胞和肠上皮黄嘌呤氧化酶产生的活性氧可能是组织损伤的最终途径。保护机制包括由组成型（主要是神经元型）一氧化氮合酶和土著益生菌（如双歧杆菌）产生的一氧化氮。前者维持肠道灌注和粘膜屏障的完整性，后者保持有毒细菌的检查。组织损伤的发展取决于损伤机制和保护机制之间的平衡。
Necrotizing enterocolitis (NEC), a disease affecting predominantly premature infants, is a leading cause of morbidity and mortality in neonatal intensive care units. Although several predisposing factors have been identified, such as prematurity, enteral feeding, and infection, its pathogenesis remains elusive. In the past 20 years, we have established several animal models of NEC in rats and found several endogenous mediators, especially platelet-activating factor (PAF), which may play a pivotal role in NEC. Injection of PAF induces intestinal necrosis, and PAF antagonists prevent the bowel injury induced by bacterial endotoxin, hypoxia, or challenge with tumor necrosis factor-a (TNF) plus endotoxin in adult rats. The same is true for lesions induced by hypoxia and enteral feeding in neonatal animals. Human patients with NEC show high levels of PAF and decreased plasma PAF-acetylhydrolase, the enzyme degrading PAF. The initial event in our experimental models of NEC is probably polymorphonuclear leukocyte (PMN) activation and adhesion to venules in the intestine, which initiates a local inflammatory reaction involving proinflammatory mediators including TNF, complement, prostaglandins, and leukotriene C4. Subsequent norepinephrine release and mesenteric vasoconstriction result in splanchnic ischemia and reperfusion. Bacterial products (e.g., endotoxin) enter the intestinal tissue during local mucosal barrier breakdown, and endotoxin synergizes with PAF to amplify the inflammation. Reactive oxygen species produced by the activated leukocytes and by intestinal epithelial xanthine oxidase may be the final pathway for tissue injury. Protective mechanisms include nitric oxide produced by the constitutive (mainly neuronal) nitric oxide synthase, and indigenous probiotics such as Bifidobacteria infantis. The former maintains intestinal perfusion and the integrity of the mucosal barrier, and the latter keep virulent bacteria in check. The development of tissue injury depends on the balance between injurious and protective mechanisms.
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影响因子：
2.9
作者：
CAPLAN, M;HSUEH, W;DONOVAN, M
通讯作者：
DONOVAN, M
影响因子：
24.5
作者：
CUEVA, JP;HSUEH, W
通讯作者：
HSUEH, W
DOI：
10.1084/jem.166.5.1390
发表时间：
1987-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Camussi G;Bussolino F;Salvidio G;Baglioni C
通讯作者：
Baglioni C
DOI：
10.3109/15513819409037698
发表时间：
1994-11-01
期刊：
PEDIATRIC PATHOLOGY
影响因子：
--
作者：
CAPLAN, MS;HEDLUND, E;HSUEH, W
通讯作者：
HSUEH, W
影响因子：
2.4
作者：
BARLOW, B;SANTULLI, TV;SCHULLINGER, JN
通讯作者：
SCHULLINGER, JN