Dual Roles of Endogenous Platelet-Activating Factor Acetylhydrolase in a Murine Model of Necrotizing Enterocolitis
Dual Roles of Endogenous Platelet-Activating Factor Acetylhydrolase in a Murine Model of Necrotizing Enterocolitis
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DOI：
10.1203/00006450-201011001-00439
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发表时间：
2010-09-01
影响因子：
3.6
通讯作者：
Caplan, Michael
中科院分区：
文献类型：
--
作者：
Lu, Jing;Pierce, Marissa;Caplan, Michael
Human preterm infants with necrotizing enterocolitis (NEC) have increased circulating and luminal levels of platelet-activating factor (PAF) and decreased serum PAF-acetylhydrolase (PAF-AH), the enzyme that inactivates PAF. Formula supplemented with recombinant PAF-AH decreases NEC in a neonatal rat model. We hypothesized that endogenous PAF-AH contributes to neonatal intestinal homeostasis and therefore developed PAF-AH(-/-) mice using standard approaches to study the role of this enzyme in the neonatal NEC model. After exposure to a well-established NEC model, intestinal tissues were evaluated for histology, proinflammatory cytokine mRNA synthesis, and death using standard techniques. We found that mortality rates were significantly lower in PAF-AH(-/-) pups compared with wild-type controls before 24 h of life but surviving PAF-AH(-/-) animals were more susceptible to NEC development compared with wild-type controls. Increased NEC incidence was associated with prominent inflammation characterized by elevated intestinal mRNA expression of sPLA(2), inducible NOS, and CXCL1. In conclusion, the data support a protective role for endogenous PAF-AH in the development of NEC, and because preterm neonates have endogenous PAF-AH deficiency, this may place them at increased risk for disease. (Pediatr Res 68: 225-230, 2010)
