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  • 标题:Gestational Exposure of Mice to Secondhand Cigarette Smoke Causes Bronchopulmonary Dysplasia Blocked by the Nicotinic Receptor Antagonist Mecamylamine
  • 本地全文:下载
  • 作者:Shashi P. Singh ; Sravanthi Gundavarapu ; Kevin R. Smith
  • 期刊名称:Environmental Health Perspectives
  • 印刷版ISSN:0091-6765
  • 电子版ISSN:1552-9924
  • 出版年度:2013
  • 卷号:121
  • 期号:8
  • 页码:957-964
  • DOI:10.1289/ehp.1306611
  • 出版社:OCR Subscription Services Inc
  • 摘要:ackground:Cigarette smoke (CS) exposure during gestation may increase the risk of broncho-pulmonary dysplasia (BPD)—a developmental lung condition primarily seen in neonates that is characterized by hypoalveolarization, decreased angio genesis, and diminished surfactant protein production and may increase the risk of chronic obstructive pulmonary disease. oBjective:We investigated whether gestational exposure to secondhand CS (SS) induced BPD and sought to ascertain the role of nicotinic acetylcholine receptors (nAChRs) in this response.Methods:We exposed BALB/c and C57BL/6 mice to filtered air (control) or SS throughout the ges-tation period or postnatally up to 10 weeks. Lungs were examined at 7 days, 10 weeks, and 8 months after birth. results:Gestational but not postnatal exposure to SS caused a typical BPD-like condition: sup-pressed angio genesis [decreased vascular endothelial growth factor (VEGF), VEGF receptor, and CD34/CD31 (hematopoietic progenitor cell marker/endothelial cell marker)], irreversible hypoalveolari zation, and significantly decreased levels of Clara cells, Clara cell secretory protein, and surfactant proteins B and C, without affecting airway ciliated cells. Importantly, concomitant exposure to SS and the nAChR antagonist mecamylamine during gestation blocked the develop-ment of BPD.conclusions:Gestational exposure to SS irreversibly disrupts lung development leading to a BPD-like condition with hypoalveolarization, decreased angio genesis, and diminished lung secretory function. Nicotinic receptors are critical in the induction of gestational SS–induced BPD, and the use of nAChR antagonists during pregnancy may block CS-induced BPD.
  • 关键词:angio ;genesis; bronchopulmonary dysplasia; cigarette smoke; nicotinic receptors; ;secretory/ ;surfactant proteins
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