The role of platelet activating factor in a neonatal piglet model of necrotising enterocolitis
The role of platelet activating factor in a neonatal piglet model of necrotising enterocolitis
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DOI：
10.1136/gut.2003.024521
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发表时间：
2004-02-01
期刊：
影响因子：
24.5
通讯作者：
Booth, IW
中科院分区：
文献类型：
--
作者：
Ewer, AK;Al-Salti, W;Booth, IW
背景和目的：坏死性小肠结肠炎（NEC）是早产儿的一种潜在破坏性疾病，但其病因尚不清楚。这些研究的目的是建立新生仔猪NEC模型，然后使用该模型研究血小板活化因子（PAF）在其发病机制中的作用。（i）对照组，和经受（ii）缺氧、（iii）脂多糖（LPS）、（iv）缺氧+LPS、（v）缺氧+LPS和PAF拮抗剂WEB 2170的组，和（vi）PAF。记录动脉血压（ABP）、上级肠系膜动脉血流量（MBF）、肠系膜血管传导性（MVC）和动脉血气，并进行肠组织学检查。结果：LPS、低氧+LPS或PAF均可引起出血性肠病变，并伴有不同程度的肠损伤。PAF引起MVC和MBF的显著初始降低，而缺氧+LPS引起ABP和MBF的显著晚期降低，并且有MVC降低的趋势。结论：缺氧+LPS或PAF可引起新生仔猪血液动力学改变和肠损伤，与NEC的病理学特征一致。这些作用通过预先给予WEB 2170而改善，表明PAF在NEC的发病机制中起重要作用。
Background and aims: Necrotising enterocolitis (NEC) is a potentially devastating disorder of preterm infants but its aetiology remains unclear. The aim of these studies was to develop a neonatal piglet model for NEC and to then use the model to investigate the role of platelet activating factor (PAF) in its pathogenesis.Methods: Anaesthetised newborn piglets were divided into six groups: (i) controls, and groups subjected to (ii) hypoxia, (iii) lipopolysaccharide (LPS), (iv) hypoxia+LPS, ( v) hypoxia+LPS and the PAF antagonist WEB 2170, and ( vi) PAF. Arterial blood pressure (ABP), superior mesenteric artery blood flow (MBF), mesenteric vascular conductance (MVC), and arterial blood gases were recorded, and intestinal histology was evaluated.Results: Exposure to LPS, hypoxia+LPS, or PAF all caused haemorrhagic intestinal lesions associated with varying degrees of intestinal injury. PAF caused a significant initial decrease in both MVC and MBF whereas hypoxia+LPS caused a significant late reduction in ABP and MBF with a trend towards a decrease in MVC. The effects of hypoxia+LPS on both haemodynamic changes and intestinal injury were ameliorated by WEB 2170.Conclusions: Administration of hypoxia and LPS or of PAF in the neonatal piglet induces haemodynamic changes and intestinal lesions that are consistent with NEC. These effects are ameliorated by prior administration of WEB 2170, indicating an important role for PAF in the pathogenesis of NEC.