Determining the cellular mechanisms involved in the airway response to topical citrate

确定局部柠檬酸盐气道反应中涉及的细胞机制

• 批准号: nhmrc : 457572
• 负责人: A/Pr Peter Middleton
• 金额: $ 29.64万
• 依托单位: The University of Sydney
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/determining-cellular-mechanisms-topical-citrate/94883
• 关键词: Determining; cellular; mechanisms; involved; airway

The air passages of the lungs are lined by mucous membranes. These membranes are covered by a thin layer of fluid to protect the airways from drying. This fluid allows the cilia, the hair like projections on top of the airway cells to beat more effectively to remove mucous and inhaled particles from the lungs. The volume and composition of this fluid is determined by the salt and water movement across the mucous membranes of the airways. These processes are abnormal in cystic fibrosis (CF), the most common lethal inherited disease affecting Australians. In CF, an abnormal gene disrupts one of the major mechanisms for salt and water movement in the air passages. This abnormal salt transport causes drying of the airway surface which impairs the working of the cilia. This leads to retention of mucous in the airways with repeated bacterial infections damaging the lungs. Over the last 10 years, we have developed a series of simple tests to measure the abnormalities in the CF airway of human subjects. We have isolated an exciting new clinical application for sodium citrate, a substance used in blood transfusions. Citrate appears to alter both the salt transport abnormalities found in CF. This research proposal seeks to better understand the dual effects of citrate and to test similar compounds that may have stronger effects. The ultimate aim of our research is to have sufficient knowledge to work out the best way to develop a new treatment for CF.

肺部的气道由粘膜构成。这些薄膜被一层薄薄的液体覆盖，以保护呼吸道不会干燥。这种液体允许纤毛，也就是呼吸道细胞顶部的毛发状突起，更有效地跳动，从肺部清除粘液和吸入的颗粒。这种液体的体积和组成是由跨越呼吸道粘膜的盐和水的运动决定的。这些过程在囊性纤维化(CF)中是异常的，这是影响澳大利亚人的最常见的致命遗传病。在慢性阻塞性肺疾病中，一种异常基因扰乱了空气通道中盐分和水分运动的主要机制之一。这种异常的盐分运输导致呼吸道表面干燥，从而损害纤毛的工作。这会导致粘液滞留在呼吸道，反复的细菌感染会损害肺部。在过去的10年里，我们已经开发了一系列简单的测试来测量人类受试者CF气道的异常。我们分离出了一种令人兴奋的柠檬酸钠临床应用，这是一种用于输血的物质。柠檬酸似乎改变了在CF中发现的盐分运输异常。这项研究计划旨在更好地了解柠檬酸盐的双重作用，并测试可能具有更强作用的类似化合物。我们研究的最终目的是有足够的知识来找出开发治疗CF的新方法的最佳方法。