The role of recombinant platelet-activating factor acetylhydrolase in a neonatal rat model of necrotizing enterocolitis
The role of recombinant platelet-activating factor acetylhydrolase in a neonatal rat model of necrotizing enterocolitis
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DOI：
10.1203/00006450-199712000-00010
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发表时间：
1997-12-01
影响因子：
3.6
通讯作者：
Yu, A
中科院分区：
文献类型：
--
作者：
Caplan, MS;Lickerman, M;Yu, A
研究表明，内源性炎症介质血小板活化因子（PAF）在新生儿坏死性小肠结肠炎（NEC）的病理生理过程中起重要作用。本研究旨在探讨PAF降解酶乙酰水解酶（PAF-AH）在新生大鼠NEC模型中的作用。为研究重组人血小板活化因子AH（rPAF-AH）的吸收、定位和活性，新生大鼠经肠给予rPAF-AH后，分别于8 h和24 h取血浆和小肠，用酶联免疫法测定血浆和小肠中rPAF-AH的酶活性和rPAF-AH的浓度。为了研究rPAF-AH对新生儿NEC的影响，每3小时通过肠内途径用rPAF-AH处理大鼠，然后根据建立的新生大鼠NEC方案进行配方饲料喂养和窒息。与对照组相比，肠内rPAF-AH预处理显著降低了NEC的发生率（6/26 vs 19/26，p < 0.001）。我们发现，肠内rPAF-AH管理导致显着的肠PAF-AH活动，但没有循环PAF-AH活动，尽管免疫组织化学定位的管理rPAF-AH肠上皮细胞。这些结果表明，rPAF-AH在新生大鼠肠道中是功能性的和稳定的。我们的结论是，肠内给予rPAF-AH仍然是局部活性，并降低了NEC的发生率在我们的实验动物模型。
Previous studies have shown that the endogenous inflammatory mediator platelet-activating factor (PAF) plays an important role in the pathophysiology of neonatal necrotizing enterocolitis (NEC). This study was designed to investigate the role of the PAF-degrading enzyme acetylhydrolase (PAF-AH) in a neonatal rat model of NEC. To study the absorption, localization, and activity of human recombinant PAF-AH (rPAF-AH), newborn rats were treated with enteral rPAF-AH, and plasma and intestines were sampled at 8 and 24 h for determination of PAF-AH enzyme activity and rPAF-AH concentration using a specific enzyme-linked immunoassay. To study the effect of rPAF-AH on neonatal NEC, rats were treated with rPAF-AH via the enteral route every 3 h, and then subjected to formula feeding and asphyxia per an established neonatal rat protocol for NEC. Pretreatment with enteral rPAF-AH significantly reduced the incidence of NEC compared with controls (6/26 versus 19/26, p < 0.001). We found that enteral rPAF-AH administration resulted in significant intestinal PAF-AH activity but no circulating PAF-AH activity despite immunohistochemical localization of the administered rPAF-AH to the intestinal epithelial cells. These findings suggest that rPAF-AH is functional and stable in the gut of neonatal rats. We conclude that enteral administration of rPAF-AH remains locally active and reduces the incidence of NEC in our experimental animal model.