Choi Chang Won, Lee Juyoung, Oh Joo Youn, Lee Seung Hyun, Lee Hyun Ju, Kim Beyong Il
Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Pediatr Res. 2016 Feb;79(2):287-94. doi: 10.1038/pr.2015.224. Epub 2015 Nov 9.
Prenatal or postnatal systemic inflammation can contribute to the development of bronchopulmonary dysplasia (BPD). We investigated whether prenatal intra-amniotic (i.a.) inflammation or early postnatal systemic inflammation can induce BPD in a rat model.
One microgram of lipopolysaccharide (LPS) or vehicle was injected into the amniotic sacs 2 d before delivery (E20). After birth, 0.25 mg/kg of LPS or vehicle was injected into the peritoneum of pups on postnatal day (P)1, P3, and P5. On P7 and P14, peripheral blood (PB), bronchoalveolar lavage fluid (BALF), and lung tissue were obtained and analyzed.
Postnatal i.p. injections of LPS significantly increased neutrophil counts in PB and BALF on P7 and P14. Similarly, proinflammatory cytokine and angiogenic factor transcript levels were increased in the lung by i.p. LPS on P7. Alveolar and pulmonary vascular development was markedly disrupted by i.p. LPS on P14. However, pretreatment with i.a. LPS significantly negated the detrimental effects of postnatal i.p. LPS on PB and BALF neutrophil counts and on lung proinflammatory cytokine expression and histopathological changes.
Exposure to early postnatal systemic LPS induces BPD, an arrest in alveolarization, in neonatal rats. Preceding exposure to i.a. LPS protects the lungs against BPD triggered by postnatal systemic inflammation.
产前或产后全身性炎症可促使支气管肺发育不良(BPD)的发生。我们研究了产前羊膜内(i.a.)炎症或产后早期全身性炎症是否能在大鼠模型中诱导BPD。
在分娩前2天(E20),将1微克脂多糖(LPS)或赋形剂注入羊膜囊。出生后,在出生后第(P)1天、P3天和P5天,将0.25毫克/千克的LPS或赋形剂注入幼崽的腹腔。在P7和P14时获取外周血(PB)、支气管肺泡灌洗液(BALF)和肺组织并进行分析。
产后腹腔注射LPS显著增加了P7和P14时PB和BALF中的中性粒细胞计数。同样,腹腔注射LPS使P7时肺中促炎细胞因子和血管生成因子的转录水平升高。腹腔注射LPS在P14时显著破坏了肺泡和肺血管的发育。然而,产前羊膜内注射LPS预处理显著抵消了产后腹腔注射LPS对PB和BALF中性粒细胞计数以及肺促炎细胞因子表达和组织病理学变化的有害影响。
出生后早期全身性暴露于LPS可诱导新生大鼠发生BPD,即肺泡化停滞。产前暴露于羊膜内LPS可保护肺免受产后全身性炎症引发的BPD影响。