LUNG GAS-EXCHANGE SURFACE--FORMATION AND REGULATION

肺气体交换表面——形成和调节

• 批准号: 3353523
• 负责人: GLORIA D MASSARO
• 金额: $ 22.31万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-15 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3353523
• 关键词: albino rat; bronchioles; cell growth regulation; combination chemotherapy; dexamethasone; electron microscopy; embryo /fetus toxicology; embryogenesis; gestational age; histogenesis; hormone regulation /control mechanism; lung alveolus; mammalian embryology; mature animal; newborn animals; oxygen consumption; photography; pleural cavity; respiratory epithelium; respiratory gas transport; stainings; surface property; thyroid hormones; tissue /cell preparation

Thinning, septation, and change in cellular composition of the saccules that compose the gas-exchange region of the immature lung, and the postseptation increase in alveolar number and average alveolar volume, effect the relation between the gas-exchange surface area (Sa) and the organism's metabolic rate (VO2). Our studies demonstrate, or are consistent with, the following new information and ideas: 1) means "other" than septation produce most alveoli formed during the period of "septation"; 2) dexamethasone (Dex) treatment during septation irrevocably blocks septation, and slows the rate of "other" means of forming alveoli even after Dex-treatment is stopped; 3) the Dex-induced effects include the premature completion of the seemingly normal changes in the relative cellular composition of the alveolar wall; 4) clinically relevant short- term prenatal treatment with Dex does not affect Sa at birth but is expressed as diminished postnatal increase in Sa; 5) thyroid hormone, in doses that do not increase VO2, accelerates the postnatal increase of Sa. We will continue to take advantage of new stereological methods to: 1) test the hypothesis that short-term (3 days) Dex treatment in late gestation or during the period of "septation" can prematurely and permanently terminate (or diminish) septation or "other" means of forming alveoli and that this effect occurs with premature completion of the normal developmental evolution of the absolute cellular composition of the gas- exchange wall; 2) determine the architectural mechanism by which thyroid hormone, in non-calorigenic doses, accelerates the early postnatal increase in Sa, elucidate its effect on the cellular composition of the gas-exchange wall (contrasting it with the effect of Dex), and, test if thyroid hormone can overcome the Dex-impairment of alveolus formation and increase of Sa; 3) "mark" already formed lung to test if, after septation, new alveolus formation occurs mainly at the alveolar-pleural interface. We think our prior results show the feasibility of our approach, and, the strong likelihood we will provide substantial new insights into a neglected but physiologically and clinically important aspect of lung development.

变薄、分隔和囊泡细胞组成的变化 组成未成熟肺的气体交换区， 隔后肺泡数和平均肺泡容积增加， 影响气体交换表面积（Sa）与 代谢率（VO 2）。 我们的研究表明， 与之一致，以下新信息和想法：1）表示“其他” 比分隔产生大多数肺泡形成期间， “分隔”; 2）地塞米松（Dex）治疗期间分隔 阻止分隔，并减缓形成肺泡的“其他”方式的速度 即使在停止Dex治疗后; 3）Dex诱导的效应包括 过早完成看似正常的相对变化 肺泡壁的细胞组成; 4）临床相关的短- 足月产前Dex治疗不影响出生时Sa， 表示为Sa的出生后增加减少; 5）甲状腺激素， 不增加VO 2的剂量加速了Sa的出生后增加。 我们将继续利用新的体视学方法：1） 检验短期（3天）地塞米松治疗在晚期 妊娠期或在“分隔”期间， 永久终止（或减少）分隔或“其他”形成方式 肺泡，这种影响发生与过早完成的正常 气体的绝对细胞组成的发展演变- 交换壁; 2）确定甲状腺的结构机制， 激素，在非产热剂量，加速出生后早期的增加 在Sa中，阐明其对气体交换的细胞组成的影响 壁（对比它与地塞米松的作用），并测试，如果甲状腺激素 能克服Dex对肺泡形成的损害和Sa的增加; 3)“标记”已形成肺测试，分隔后，新的肺泡 形成主要发生在肺泡-胸膜界面。 我们认为我们的 先前的结果表明，我们的方法的可行性，和，强 我们可能会为一个被忽视但 肺发育的生理和临床重要方面。