PATHOBIOLOGY OF BRONCHOPULMONARY DYSPLASIA

目的：本研究假设BPD是未成熟肺损伤和异常修复的结果。我们推测参与BPD发病的因素包括肺表面活性物质蛋白的异常(先天或后天)、氧化应激、炎症和细胞迁移、结缔组织中胰岛素样生长因子(IGF)和弹性蛋白成分的变化，以及伴随血管重塑的肺动脉高压。目的1：建立一个具有广泛的临床数据库和生物统计学支持的新生儿肺部疾病临床样本库，使SCOR项目中的基础科学研究人员能够检验有关BPD发病机制的假说。目的：探讨肺表面活性物质蛋白-B(SP-B)的发育缺陷是否与呼吸窘迫和BPD的发生有关，并研究与SP-B遗传性缺陷相关的代谢异常。目的：探讨BPD早产儿血浆过氧亚硝酸盐介导的氧化应激标志物--硝基酪氨酸水平是否升高。目的：测定肺部疾病插管儿支气管肺泡灌洗(BAL)、血和尿液中炎症过程的关键成分(细胞成分、诱导型一氧化氮合酶(INOS)、透明质酸(HA)和HA介导的运动能力受体(RAMM)以及部分细胞因子)的时间变化，并将这些变化与其临床病程相关联。目的5：观察RDS和BPD患儿肺组织胰岛素样生长因子轴的变化。目的6：通过测定BAL标本中弹性蛋白衍生多肽的含量来确定弹性蛋白的降解与BPD的临床病程之间是否存在关系。目的：探讨RDS和BPD患儿出生后血浆内皮素-1水平的正常下降是否延迟。

AIMS: The hypothesis of this study is that BPD is the result of injury and abnormal repair to an immature lung. We hypothesize that factors involved in the pathogenesis of BPD include abnormalities (congenital or acquired) of the surfactant proteins, oxidative stress, inflammation and cell migration, changes in insulin-like growth factors (IGF's) and elastin components of connective tissue, and pulmonary hypertension with vascular remodeling. AIM 1: To create a Clinical Sample Bank of neonates with lung disease, some of whom will progress to the development of BPD, with a broad clinical database and biostatistical support, to allow basic science investigators in the SCOR project to test hypotheses regarding the pathogenesis of BPD. AIM 2: To determine whether a developmental deficiency of surfactant protein-B (SP-B) contributes to the occurrence of respiratory distress and BPD, and to study metabolic abnormalities associated with inherited deficiency of SP-B. AIM 3: To determine whether plasma nitrotyrosine levels, a marker of peroxynitrite mediated oxidant stress, are elevated in premature infants who develop BPD. AIM 4: To measure the temporal changes in critical components of the inflammatory process (cell composition, inducible nitric oxide synthase (iNOS), hyaluronan (HA), and Receptor for HA-mediated mobility (RHAMM), and selected cytokines) in bronchoalveolar lavage (BAL), blood, and urine samples obtained from intubated infants with lung disease, and to correlate these changes with their clinical course. AIM 5: To examine changes in the IGF axis that occurs in lungs of infants with RDS and BPD. AIM 6: To determine whether there is a relationship between degradation of elastin, as determined by assay of elastin-derived peptides in BAL samples, and the clinical course of BPD. AIM 7: To determine whether the normal fall in plasma endothelin-1 concentrations after birth are delayed in infants with RDS and BPD.