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早产羔羊慢性脲原体感染肺血管和肺泡发育的研究

Pulmonary vascular and alveolar development in preterm lambs chronically colonized with Ureaplasma parvum.

机构信息

The University of Western Australia, Perth, Australia.

出版信息

Am J Physiol Lung Cell Mol Physiol. 2010 Aug;299(2):L232-41. doi: 10.1152/ajplung.00369.2009. Epub 2010 May 21.

Abstract

Ureaplasma species, the most commonly isolated microorganisms in women with chorioamnionitis, are associated with preterm delivery. Chorioamnionitis increases the risk and severity of bronchopulmonary dysplasia and persistent pulmonary hypertension in newborns. It is not known whether the timing of exposure to inflammation in utero is an important contributor to the pathogenesis of bronchopulmonary dysplasia. We hypothesized that chronic inflammation would alter the pulmonary air space and vascular development after 70 days of exposure to infection. Pregnant ewes were given intra-amniotic injection of Ureaplasma parvum serovars 3 or 6 at low (2 x 10(4) cfu) or high doses (2 x 10(7) cfu) or media (controls) at 55 days gestational age. Fetuses were delivered at 125 days (term = 150 days). U. parvum was grown from the lungs of all exposed fetuses, and neutrophils and monocytes were increased in the air spaces. Lung mRNA expression of IL-1beta and IL-8, but not IL-6, was modestly increased in U. parvum-exposed fetuses. U. parvum exposure increased surfactant and improved lung gas volumes. The changes in lung inflammation and maturation were independent of serovar or dose. Exposure to U. parvum did not change multiple indices of air space or vascular development. Parenchymal elastin and collagen content were similar between groups. Expression of several endothelial proteins and pulmonary resistance arteriolar media thickness were also not different between groups. We conclude that chronic exposure to U. parvum does not cause sustained effects on air space or vascular development in premature lambs.

摘要

解脲脲原体属,在绒毛膜羊膜炎患者中最常分离到的微生物,与早产有关。绒毛膜羊膜炎增加了新生儿支气管肺发育不良和持续性肺动脉高压的风险和严重程度。尚不清楚胎儿宫内暴露于炎症的时间是否是支气管肺发育不良发病机制的重要因素。我们假设慢性炎症会改变感染后 70 天的肺气道和血管发育。在妊娠第 55 天,给怀孕的母羊羊膜内注射低剂量(2×10^4cfu)或高剂量(2×10^7cfu)解脲脲原体 3 或 6 血清型或培养基(对照)。在 125 天(足月= 150 天)分娩胎儿。从所有暴露的胎儿肺部中培养出解脲脲原体,并且气道中中性粒细胞和单核细胞增加。解脲脲原体暴露的胎儿肺组织中 IL-1β和 IL-8 的 mRNA 表达适度增加,但 IL-6 没有增加。解脲脲原体暴露增加了表面活性剂并改善了肺气体容积。气道和血管发育的改变与血清型或剂量无关。解脲脲原体暴露并未改变气道或血管发育的多个指标。肺实质弹力蛋白和胶原蛋白含量在各组之间相似。几组内皮蛋白的表达和肺阻力小动脉中膜厚度在各组之间也没有差异。我们的结论是,慢性暴露于解脲脲原体不会对早产羔羊的气道或血管发育产生持续影响。

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