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描述(由申请人提供):肺表面活性剂降低肺表面张力。II型肺细胞合成并分泌一种脂质和蛋白质的混合物,它们共同起着表面活性剂的作用,吸附在肺泡周围的薄液体层的空气/水界面上,降低表面张力。肺表面活性物质的功能是维持正常呼吸所必需的。当表面张力升高时,通气损伤肺部,破坏分隔肺泡空气和毛细血管血液的薄屏障。这种损伤会导致肺水肿和呼吸衰竭。由表面张力升高引起的最明确的疾病是呼吸窘迫综合征,在这种情况下,早产儿在表面活性剂达到正常水平之前出生。最确凿的证据表明,表面活性剂缺乏导致的障碍是提高存活率的结果,这些婴儿治疗外源性表面活性剂。然而,这些药物中最有效的是从动物身上获得的,而且这些表面活性剂没有足够的量用于治疗与表面活性剂异常有关的其他疾病的成年人。我们的研究重点是表面活性剂囊泡吸附到界面上的过程。疏水表面活性剂蛋白的缺乏,促进表面活性剂膜的快速形成,导致RDS,尽管表面活性剂脂质的正常水平。这些结果证明了组分吸附到界面的过程的基本重要性。吸附发生的机制是我们研究的重点。相关性:肺表面活性剂在肺的小肺泡气囊上形成一层薄膜。在没有这些膜的情况下,通气过程损伤了肺泡空气空间和毛细血管血液之间的薄屏障,导致空气空间充血和呼吸衰竭。这项研究将确定表面活性剂薄膜是如何形成的,从而为理解肺部疾病发生的原因和治疗方法奠定基础。
英文摘要
DESCRIPTION (provided by applicant): Pulmonary surfactant lowers surface tension in the lungs. The type II pneumocyte synthesizes and secretes a mixture of lipids and proteins that together act as a surfactant, adsorbing to the air/water interface of the thin liquid layer that lines the alveoli and lowering surface tension. The function of pulmonary surfactant is essential for normal breathing. When surface tension is elevated, ventilation injures the lungs, damaging the thin barrier that separates alveolar air from capillary blood. The injury leads to pulmonary edema and respiratory failure. The best defined disorder caused by elevated surface tension is the Respiratory Distress Syndrome, in which premature infants are born prior to developing normal levels of surfactant. The most conclusive evidence that deficient surfactant causes the disorder is the improved survival that results from treating these infants with exogenous surfactant. The most effective of these agents, however, are obtained from animals, and these surfactant are unavailable in sufficient amounts for treating adults with other disorders related to abnormal surfactant. Our studies focus on the process by which surfactant vesicles adsorb to the interface. The absence of the hydrophobic surfactant proteins, which promote the rapid formation of the surfactant film, leads to RDS, despite normal levels of the surfactant lipids. These results demonstrate the fundamental importance of the process by which constituents adsorb to the interface. The mechanisms by which adsorption occurs is the focus of our studies. Relevance: Pulmonary surfactant forms a thin films that lines the small alveolar air sacks of the lungs. In the absence of these films, the process of ventilation injures the thin barrier between the alveolar air space and the capillary blood, leading to the flooding of the air spaces and respiratory failure. This research will determine how the surfactant films form to promote the basis for understanding why pulmonary diseases occur and how they can be treated.
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Therapeutic Surfactants
STRUCTURAL EFFECTS OF HYDROPHOBIC SURFACTANT PROTEINS
  • 批准号:
    8362124
  • 项目类别:
  • 资助金额:
    $0.55万
  • 财政年份:
    2011
  • 负责人:
    STEPHEN B HALL
  • 依托单位:
STRUCTURAL EFFECTS OF HYDROPHOBIC SURFACTANT PROTEINS
  • 批准号:
    8170041
  • 项目类别:
  • 资助金额:
    $0.37万
  • 财政年份:
    2010
  • 负责人:
    STEPHEN B HALL
  • 依托单位:
STRUCTURAL EFFECTS OF HYDROPHOBIC SURFACTANT PROTEINS
  • 批准号:
    7954365
  • 项目类别:
  • 资助金额:
    $0.02万
  • 财政年份:
    2009
  • 负责人:
    STEPHEN B HALL
  • 依托单位:
海外基金