EFFECTS OF PRENATAL EXPOSURE TO NICOTINE ON PRIMATE LUNG DEVELOPMENT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 母亲吸烟是导致胎儿宫内发育迟缓和早产的主要可预防原因。最近的证据表明，发育中的肺部对母亲吸烟也高度敏感，怀孕期间吸烟会导致肺功能下降，增加呼吸系统疾病，并增加子代婴儿猝死综合征(SID)的发生率。鉴于仅在美国，怀孕期间吸烟的女性每年就有超过40万名婴儿出生，因此找到防止这些变化的方法至关重要。我们的数据显示，尼古丁是吸烟母亲所生孩子肺功能改变的原因之一。在这个项目中，恒河猴被用来表征怀孕期间长期接触低水平尼古丁对肺发育和功能的影响。本项目的目的是1)通过确定尼古丁如何影响胚胎猴肺中尼古丁受体的功能来表征尼古丁作用的分子基础；2)通过功能、形态计量、免疫组织化学和分子分析来表征胎儿尼古丁暴露对肺发育的影响；以及3)开发阻断尼古丁对肺发育影响的方法，以导致临床干预措施，可以结合怀孕吸烟者的大力戒烟计划来帮助吸烟母亲的后代。今年的进展已经确定了尼古丁作用的新的分子机制，这些机制可能广泛适用于吸烟引起的疾病。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Maternal smoking is the major preventable cause of intrauterine growth retardation and prematurity. Recent evidence shows that developing lung is also highly sensitive to maternal smoking and that smoking during pregnancy leads to decreased lung function, increased respiratory diseases and increased incidence of sudden infant death syndrome (SIDS) in the offspring. Given that every year more than 400,000 infants in the US alone are born to women who smoked during pregnancy, it is of major importance to find ways to prevent those changes. Our data shows that nicotine is one of the factors responsible for the changes in pulmonary function present in children born to smoking mothers. In this project, rhesus monkeys are used to characterize the effects of chronic exposure to low levels of nicotine throughout pregnancy on lung development and function. The purposes of this project are to 1) characterize the molecular basis for nicotine's actions by determining how nicotine effects the functioning of nicotinic receptors in fetal monkey lung; 2) characterize the effect of fetal nicotine exposure on lung development by functional, morphometric, immunohistochemical and molecular analysis; and 3) develop ways to block the effects of nicotine on lung development that can lead to clinical interventions that can be combined with vigorous smoking cessation programs in pregnant smokers in order to help the offspring of smoking mothers. Progress this year has identified new molecular mechanisms underlying the effects of nicotine that may be broadly applicable to smoking-induced disease.