Kramer Boris W, Ladenburger Andreas, Kunzmann Steffen, Speer Christian P, Been Jasper V, van Iwaarden J Freek, Zimmermann Luc J I, Gantert Markus, Garnier Yves
Department of Pediatrics, Maastricht University Hospital Center, the Netherlands.
Am J Obstet Gynecol. 2009 Feb;200(2):195.e1-10. doi: 10.1016/j.ajog.2008.09.009. Epub 2008 Dec 25.
Antenatal pulmonary inflammation is associated with reduced risk for respiratory distress syndrome but with an increased risk for bronchopulmonary dysplasia (BPD) with impaired alveogenesis.
We hypothesized that fetal systemic inflammation induced by intravenous (IV) lipopolysaccharide (LPS) would affect lung development in utero.
Twenty-one fetal sheep were instrumented (107 days gestational age). Control fetuses received saline (N = 12) and 9 in the study group received 100 ng of LPS IV 3 days after surgery. Animals were assessed for lung maturation and structure after 3 (N = 5) and 7 (N = 4) days.
Interleukin-6 concentration increased in the bronchoalveolar lavage more than 40-fold 3 days after LPS IV. Processing of pro-surfactant protein (SP)-B to mature SP-B and increased SP-B concentrations were shown 7 days after LPS IV. Deposition of elastin fibers at sites of septation was disturbed within 3 days after LPS IV.
Lung maturation and disturbed lung structure occurred after short-term exposure to fetal inflammation and suggests new targeted therapies for BPD.
产前肺部炎症与呼吸窘迫综合征风险降低相关，但与肺泡生成受损的支气管肺发育不良（BPD）风险增加相关。
我们假设静脉注射（IV）脂多糖（LPS）诱导的胎儿全身炎症会影响子宫内的肺发育。
对21只胎羊进行仪器植入（妊娠107天）。对照组胎儿接受生理盐水（n = 12），研究组9只在手术后3天接受100 ng LPS静脉注射。在3天（n = 5）和7天（n = 4）后评估动物的肺成熟度和结构。
静脉注射LPS后3天，支气管肺泡灌洗中的白细胞介素-6浓度增加了40多倍。静脉注射LPS后7天，前表面活性蛋白（SP）-B加工为成熟的SP-B，且SP-B浓度增加。静脉注射LPS后3天内，弹性纤维在分隔部位的沉积受到干扰。
短期暴露于胎儿炎症后会出现肺成熟和肺结构紊乱，这提示了针对BPD的新靶向治疗方法。
