ROLE OF BOMBESIN LIKE PEPTIDES IN LUNG DEVELOPMENT

未成熟的肺发育仍然是导致 早产儿的发病率和死亡率。这样做的目的是 该项目是为了表征蛙皮素样肽在肺中的作用 发展。蛙毒素样多肽是一大家族 最初以青蛙皮肤为特征的多肽，但后来发现 在哺乳动物中具有广泛的分布和强大的生理效应。一 蛙皮素在哺乳动物中的同源物是胃泌素释放肽(GRP)。这个 GRP在人肺发育过程中的表达及其意义 GRP刺激细胞生长的能力导致了这一假说 GRP在肺发育中起着关键作用。因为 由于缺乏良好的动物模型，以前不可能 准确测定GRP在肺发育中的作用。最近， 本实验室已证实GRP在胎猴体内的表达 肺与人类有着惊人的相似之处。因此，猴子 提供了一种动物模型来描述GRP在人肺中的作用 发展。我们现在已经开发出在子宫内给药GRP的方法 对胎猴和适宜的形态计量学、组织学和分子生物学 确定这些治疗对肺的影响的技术 发展。在初步研究中，我们治疗了怀孕的猴子 孕期55~72天，应用GRP拮抗剂和生理盐水。 GRP组大鼠肺总重量增加。GRP拮抗剂 治疗后肺总重量减少。形态计量分析显示 GRP治疗可增加上皮体积，但不影响血管内皮功能 间充质体积。进一步的分析目前正在进行中。 因此，这一初步数据的结果验证了我们的 实验模型，为今后的实验奠定了基础 确定蛙皮素样肽在灵长类动物肺中的作用 发展。

Immature lung development continues to be a major cause of morbidity and mortality in premature infants. The purpose of this project is to characterize the role of bombesin-like peptides in lung development. The bombesin-like peptides are a large family of peptides originally characterized in frog skin, but later found to have wide distribution and potent physiologic effects in mammals. One mammalian homolog of bombesin is gastrin-releasing peptide (GRP). The well documented expression of GRP in developing human lung and the ability of GRP to stimulate cellular growth has led to the hypothesis that GRP plays a critical role in lung development. Because of the lack of good animal models, it has not previously been possible to accurately determine the role of GRP in lung development. Recently, our laboratory has demonstrated that GRP expression in fetal monkey lung is strikingly similar to that of humans. Thus, the monkey provides an animal model to characterize the role of GRP in human lung development. We have now developed methods to administer GRP in utero to fetal monkeys and suitable morphometric, histologic and molecular techniques to determine the effects of these treatments on lung development. In preliminary studies we have treated pregnant monkeys from day 55 to 72 of gestation with GRP, a GRP antagonist and saline. GRP treatment increased lung total lung weight. GRP antagonist treatment decreased total lung weight. Morphometric analysis showed that GRP treatment increased epithelial volume but had no effect on mesenchymal volume. Further analyses are currently in progress. Thus, the results from this preliminary data validates our experimental model and provides the basis for future experiments to determine the role of bombesin-like peptides in primate lung development.