CORTICOSTEROID AND THYROID EFFECTS ON LUNG MATURATION

我们正在继续寻求资金，以询问以下几个问题 具有应用潜力的胎肺成熟策略 从临床上看。我们假设单次给药，直接给胎儿注射 单独或联合使用激素会导致快速而巨大的肺 对胎儿的成熟影响以前没有 被操纵了。我们计划使用激素(皮质类固醇、甲状腺激素、 表皮生长因子和转化生长因子-α)的剂量和治疗持续时间 临床上相关的。我们将在超声引导下治疗早产羊 直接给胎儿注射，然后在48小时内分娩早产羔羊 后来。将对羔羊进行广泛的出生后肺部评估。 适应时间超过4小时。生理评估将重点放在 这些测量转化为肺功能的改善。我们将衡量 肺容量、顺应性、气体交换、水肿形成和 肺对表面活性物质治疗的反应。我们还将测量 肺成熟的生化标志物--肺泡和肺组织 饱和磷脂酰胆碱池大小、肺泡表面活性物质蛋白A (SP-A)，肺组织中SP-A、SP-B和SP-C的mRNA水平。目标是 是确定一种简单的单剂量治疗策略，可以包括 不能渗透到胎盘的药物，将有效和可靠地 使胎儿的肺成熟。

We are seeking continued funding to ask a number of questions about strategies to mature the fetal lung that have the potential to be applied clinically. We hypothesize that single dose, direct fetal administration of hormones alone or in combination will cause rapid and large lung maturational effects in fetuses that have not been previously manipulated. We plan to use hormones (corticosteroids, thyroid hormones, EGF and TGF-alpha) only at doses and treatment durations that are clinically relevant. We will treat preterm sheep by ultrasound guided direct fetal injections and then deliver the preterm lambs 48 hours later. The lambs will be evaluated extensively for postnatal pulmonary adaptation over 4 hours. Physiologic assessments will focus on measurements that translate into improved lung function. We will measure lung volumes, compliances, gas exchange, edema formation, and the responses of the lungs to surfactant treatment. We also will measure biochemical markers of lung maturation - alveolar and lung tissue saturated phosphatidylcholine pool sizes, alveolar surfactant protein A (SP-A), and SP-A, SP-B, and SP-C mRNA levels in lung tissue. The goal is to identify a simple, single dose treatment strategy that can include agents not permeable to the placenta that will effectively and reliably mature the fetal lung.