PATHOBIOLOGY OF BRONCHOPULMONARY DYSPLASIA

这项研究的总体假设是，支气管肺发育不良(BPD)是未成熟肺损伤和异常修复的结果。我们推测，参与BPD发病机制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、炎症和细胞因子产生导致肺纤维化和高血压伴血管重塑。具体地说，我们认为转化生长因子b(TGFb)通过抑制表面活性物质的产生和刺激基质成分是早产儿肺炎症和纤维化的关键介质。目的1：建立早产儿肺部疾病的临床数据库和组织库，其中一些早产儿将发展为BPD。广泛的临床数据库，加上生物统计学支持，将使SCOR项目(肺发育病理生物学和BPD)的基础科学研究人员能够测试生化参数与BPD发病机制之间的联系，以及可能的治疗干预措施。目的2：探讨表面活性物质蛋白(SP-A、-B和-C)的发育缺陷水平是否与BPD的发生有关。目的：测定肺部疾病插管患儿气管抽吸物(TA)、血液和尿液中炎症细胞成分、诱导型一氧化氮合酶(INOS)、血浆硝基酪氨酸水平、透明质酸(HA)和透明质酸(HA)介导的运动受体(RAMM)以及部分细胞因子和血管活性因子的时间变化，并探讨其与临床病程的关系。

The overall hypothesis of this study is that bronchopulmonary dysplasia (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 cytokine production leading to pulmonary fibrosis and hypertension with vascular remodeling. Specifically, we propose that transforming growth factor b (TGFb) is a key mediator of inflammation and fibrosis in the premature lung through inhibition of surfactant production and stimulation of matrix constituents. AIM 1: To create a Clinical Data Base and Tissue Bank from premature neonates with lung disease, some of whom will progress to the development of BPD. The broad clinical database, along with biostatistical support, will allow basic science investigators in the SCOR project (Pathobiology of Lung Development and BPD) to test for associations between biochemical parameters and pathogenesis of BPD, as well as possible therapeutic interventions. AIM 2: To determine whether the level of developmental deficiencies of surfactant proteins (SP-A, -B and -C) contribute to the occurrence of BPD. AIM 3: To measure the temporal changes in critical components of the inflammatory process (inflammatory cell composition, inducible nitric oxide synthase (iNOS), plasma nitrotyrosine levels, hyaluronan (HA), and Receptor for HA-mediated motility (RHAMM), and selected cytokines and vasoactive factors) in tracheal aspirate (TA), blood, and urine samples obtained from intubated infants with lung disease, and to correlate these changes with their clinical course.