EFFECTS OF PRENATAL EXPOSURE TO NICOTINE ON PRIMATE LUNG DEVELOPMENT

母亲在怀孕期间吸烟的有害影响是 很好地建立了。 母亲吸烟是导致婴儿死亡的主要可预防原因。 胎儿宫内发育迟缓和早产。 也许没那么好 值得赞赏的是，最近，有力的证据表明，吸烟期间 怀孕会直接影响肺部发育。 与子宫内烟草暴露相关的呼吸系统问题包括 肺功能下降，呼吸系统疾病增加， 婴儿猝死综合症（SIDS）。 鉴于 怀孕期间吸烟的不幸流行以及由此产生的 严重后果，重要的是要了解 吸烟引起的新生儿变化的潜在机制。 我们有 开始通过给予尼古丁来研究这一点， 定时怀孕的恒河猴。 在初步研究中， 证明了怀孕的恒河猴接触尼古丁 与吸烟者一致的剂量会改变胎儿气道发育 并且相关效应可在胎猴肺器官中再现 文化 免疫组织化学显示， 而尼古丁似乎改变了这种模式 受体的表达。 初步数据进一步表明， 尼古丁的作用，通过尼古丁受体，可能是 通过拮抗肽生长的促有丝分裂作用介导 如GRP。 从这些研究中， 描述长期尼古丁暴露对肺的影响 功能，确定这些影响的程度 可逆的，并开始了解潜在的机制 这些影响。 资助中心资助项目出版物Sekhon HS，Jia Y，Kuryatov A，科尔L，Raab R，惠特塞特JA，Lindstrom J， 斯平德尔急诊室。 烟碱与烟碱胆碱能的相互作用 恒河猴胎儿肺中的受体。 Soc Neurosci Abstr 24：335， 1998. Sekhon HS，Jia Y，Kuryatov A，科尔L，Raab R，Lindstrom J， 斯平德尔急诊室。 胃泌素释放肽（GRP）与 尼古丁在灵长类动物肺部发育中的作用 在国家心肺和 血液研究所关于肺的分子胚胎学的讲习班（在 Bethesda，MD，1998年6月1日）（摘要）。

The deleterious effects of maternal smoking during pregnancy are well established. Maternal smoking is the major preventable cause of intrauterine growth retardation and prematurity. Perhaps less well appreciated, is the recent, strong evidence, that smoking during pregnancy directly and adversely affects lung development. Respiratory problems associated with in utero tobacco exposure include decreased lung function, increased respiratory diseases and increased incidence of sudden infant death syndrome (SIDS). Given the unfortunate prevalence of smoking during pregnancy and the resulting serious consequences, it is of major importance to understand the mechanisms underlying smoking-induced changes in the newborn. We have begun to investigate this by administration of nicotine to timed-pregnant rhesus monkeys. In preliminary studies we have demonstrated that exposure of pregnant rhesus monkeys to a nicotine dose consistent with that of smokers alters fetal a irway dev elopment and that related effects can be reproduced in fetal monkey lung organ culture. Immunohistochemistry shows wide expression of nicotinic receptors in developing lung and nicotine appears to alter the pattern of receptor expression. Preliminary data further suggests that some of the effects of nicotine, acting though nicotinic receptors, may be mediated by antagonism of the mitogenic effects of peptide growth factors such as GRP. From these studies will come the first description of the effects of chronic nicotine exposure on lung function, a determination of the extent to which these effects are reversible, and a beginning understanding of the mechanisms underlying these effects. FUNDING Center-supported project PUBLICATIONS Sekhon HS, Jia Y, Kuryatov A, Cole L, Raab R, Whitsett JA, Lindstrom J, Spindel ER. Interaction of nicotine with nicotinic cholinergic receptors in fetal rhesus monkey lung. Soc Neurosci Abstr 24:335, 1998. Sekhon HS, Jia Y, Kuryatov A, Cole L, Raab R, Lindstrom J, Spindel ER. Interaction between gastrin-releasing peptide (GRP) and nicotine in primate lung development. In National Heart Lung and Blood Institute workshop on Molecular Embryology of the Lung (held in Bethesda, MD, June 1, 1998) (abstract).