EFFECTS OF PRENATAL EXPOSURE TO NICOTINE ON PRIMATE LUNG DEVELOPMENT

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 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，肺的发育也对母亲吸烟高度敏感，怀孕期间吸烟导致肺功能下降，呼吸道疾病增加，后代婴儿猝死综合症的发病率增加。 鉴于每年仅在美国就有超过40万名婴儿出生于怀孕期间吸烟的妇女，因此找到防止这些变化的方法至关重要。 我们的数据表明，尼古丁是吸烟母亲所生儿童肺功能变化的因素之一。在这个项目中，恒河猴被用来描述长期暴露于低水平的尼古丁在整个怀孕期间对肺发育和功能的影响。 本项目的目的是：1）通过测定尼古丁如何影响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、形态计量学、免疫组织化学和分子分析来表征胎猴暴露尼古丁对肺发育的影响;和3）开发阻断尼古丁对肺部发育影响的方法，从而导致临床干预措施，这些干预措施可以与怀孕吸烟者的积极戒烟计划相结合，以帮助吸烟的母亲今年的进展有助于引导计划中的临床试验，以阻止母亲吸烟对胎儿发育的一些影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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 is helping lead to planned clinical trials to block some of the effects of maternal smoking on fetal development.