Maternal exposure to endotoxin delays alveolarization during postnatal rat lung development
Maternal exposure to endotoxin delays alveolarization during postnatal rat lung development
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DOI：
10.1152/ajplung.90405.2008
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发表时间：
2009-05-01
影响因子：
4.9
通讯作者：
Post, Martin
中科院分区：
文献类型：
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作者：
Cao, Lei;Wang, Jinxia;Post, Martin
曹立，王杰，Tseu I，Luo D，Post M.母体暴露于内毒素延迟出生后大鼠肺发育的肺泡形成。美国生理学杂志肺细胞分子生理学296：L726-L737，2009年。首次发表于2009年2月13日; doi：10.1152/ajplung.90405.2008。母体细菌感染通过穿过胎盘屏障并感染发育中的胎儿而对肺发育产生不利影响。对肺部发育产生负面影响的潜在机制仍不清楚。在此，我们研究了母体全身性感染是否会影响产后炎症和肺泡发育。孕鼠在第20天和第21天（足月= 22天）注射2.5 mg/kg LPS。出生后（PN 0 -21）细胞因子的mRNA和蛋白表达（IL-1 β、IL-6、IL-10、CXCL 1/2、TNF α）和涉及肺泡发生的基因[原弹性蛋白、赖氨酰氧化酶（LOX）、赖氨酰氧化酶样（LOXL）1、生腱蛋白-C（TNC）、纤蛋白5、血管内皮生长因子（VEGF-A）、VEGF受体（VEGFR）2、VEGFR 1、血小板衍生生长因子（PDGF）A、通过实时PCR和beadlyte技术定量PDGFB和PDGFR α]。在PN 0、2、6、10和14时，LPS暴露幼崽的IL-1 β、IL-6和CXCL 1/2的肺转录物和蛋白质水平显著高于对照幼崽。支气管肺泡灌洗液（BALF）的LPS暴露的动物含有显着更多的巨噬细胞在PN 2和14比对照组幼仔的BALF。形态学分析显示，与对照组幼仔相比，暴露于LPS的动物具有更少和更大的肺泡，更少的次级隔膜和降低的外周血管密度。这种肺泡发育的形态学延迟在PN 14后消失。在PN 2 -14肺中，LPS暴露动物的原弹性蛋白、LOXL 1、VEGF、VEGFR 2和PDGFR α mRNA表达显著高于对照动物。TNC、LOX、fibulin 5、VEGFR 1、PDGFA和PDGFB的表达不受母体LPS暴露的影响。总之，这些数据表明，母体暴露于内毒素导致出生后长期的肺部炎症，改变了与肺泡发生有关的分子的基因表达，并延迟了肺的形态成熟。
Cao L, Wang J, Tseu I, Luo D, Post M. Maternal exposure to endotoxin delays alveolarization during postnatal rat lung development. Am J Physiol Lung Cell Mol Physiol 296: L726-L737, 2009. First published February 13, 2009; doi:10.1152/ajplung.90405.2008.-Maternal bacterial infections adversely affect lung development by crossing the placental barrier and infecting the developing fetus. The underlying mechanism negatively affecting pulmonary development remains unknown. Herein, we investigated whether a systemic maternal infection affects postnatal inflammation and alveolar development. Pregnant rats were injected with 2.5 mg/kg LPS on day 20 and 21 (term = 22 days). Postnatal (PN0-21) mRNA and protein expression of cytokines (IL-1 beta, IL-6, IL-10, CXCL1/2, TNF alpha) and genes implicated in alveologenesis [tropoelastin, lysyl oxidase (LOX), lysyl oxidase-like (LOXL)1, tenascin-C (TNC), fibulin 5, vascular endothelial growth factor (VEGF-A), VEGF receptor (VEGFR) 2, VEGFR1, platelet-derived growth factor (PDGF) A, PDGFB, and PDGFR alpha] were quantified by real-time PCR and beadlyte technology. Lung transcript and protein levels of IL-1 beta, IL-6, and CXCL1/2 were significantly greater in LPS-exposed pups than those of control pups at PN0, 2, 6, 10, and 14. Bronchoalveolar lavage fluid (BALF) of LPS-exposed animals contained significantly more macrophages at PN2 and 14 than BALF of control pups. Morphometric analysis revealed that LPS-exposed animals had fewer and larger alveoli, fewer secondary septa, and decreased peripheral vessel density when compared with control pups. This morphological delay in alveolar development disappeared after PN14. Tropoelastin, LOXL1, VEGF, VEGFR2, and PDGFR alpha mRNA expression of LPS-exposed animals was significantly greater than those of control animals in PN2-14 lungs. TNC, LOX, fibulin 5, VEGFR1, PDGFA, and PDGFB expression was not affected by maternal LPS exposure. Together, the data demonstrate that maternal exposure to endotoxin results in a prolonged pulmonary inflammation postnatally, altered gene expression of molecules implicated in alveologenesis, and delayed morphological maturation of the lung.