ACT 2 PROJ 1: EFFECTS OF DIETARY SELENIUM ON THE DEVELOPMENT OF ASTHMA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 据估计，美国有3100万人患有哮喘。非洲裔美国人和其他少数族裔群体在哮喘患者中的比例过高。最近的数据表明，膳食中的硒(Se)是一种有效的抗氧化剂，可能在预防哮喘方面发挥重要作用。这项研究的长期目标是减少人类因哮喘而遭受的痛苦和健康差距。该项目的目标是利用小鼠模型来确定饮食中的硒水平如何影响急性和慢性哮喘的发展。确定膳食硒和哮喘之间的关系将为最终的人类临床试验提供强有力的科学框架。通过肺组织切片的组织学、细支气管灌洗以建立细胞和细胞因子谱、参与哮喘和呼吸道重塑的各种因子的mRNA和蛋白水平以及细支气管灌洗液和血清中的抗卵白蛋白抗体水平来评估哮喘在小鼠模型中的发展。使用这些方法，我们已经在一项旨在检查急性哮喘的实验中证明了硒摄入量和哮喘并不是以简单的剂量-反应方式相关。也就是说，我们已经表明，中硒组的小鼠表现出最严重的哮喘，而那些喂食低硒或高硒的小鼠患上不那么严重的哮喘。这些结果可能有助于解释人类研究中不一致的发现，这些研究未能确定膳食硒和哮喘之间的关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Asthma affects an estimated 31 million people in the United States. African Americans and other ethnic minority groups are disproportionately over-represented among those suffering with asthma. Recent data have suggested that dietary selenium (Se), a potent antioxidant, may play an important role in the prevention of asthma. The long-term goal of this research is to reduce the human suffering and health disparities from asthma. The objective of the project is to employ a mouse model to determine how levels of dietary selenium affect the development of acute and chronic asthma. Determining the relationship between dietary Se and asthma would provide a strong scientific framework for eventual clinical trials in humans. The development of asthma in the mouse model is evaluated by: histology of lung tissue sections; bronchiolar lavage to establish cellular and cytokine profiles; mRNA and protein levels of various factors involved in asthma and airway remodeling; and levels of anti-ovalbumin antibodies in bronchiolar lavage and serum. Using these measures, we have demonstrated that Se intake and asthma are not related in a simple dose-response manner in an experiment designed to examine acute asthma. That is, we have shown that mice in the medium-Se group exhibit the most severe asthma, while those fed low or high Se develop less severe asthma. These results may help to explain inconsistent findings in human studies that failed to establish the relationship between dietary Se and asthma.