项目名称: β2肾上腺素受体自身抗体在慢性阻塞性肺疾病气道重构中的作用
项目编号: No.81470235
项目类型: 面上项目
立项/批准年度: 2015
项目学科: 医药、卫生
项目作者: 贺蓓
作者单位: 北京大学
项目金额: 70万元
中文摘要: 慢性炎症反应和气道重构是慢性阻塞性肺疾病(COPD)气流受限进行性发展的重要基础。近年来随着对COPD患者肺组织中淋巴滤泡和血清中多种自身抗体的发现, 体液免疫在COPD炎症反应中的作用受到更多关注。我们的前期研究发现,在COPD患者血浆中抗β2肾上腺素受体自身抗体(β2-AAbs)水平升高,且与临床症状恶化显著相关。进一步研究证实,香烟烟雾暴露大鼠血清β2-AAbs水平随熏烟时长升高,其高峰出现早于气流受限。体外研究发现β2-AAbs可能具有类激动剂样作用。本项目拟在前期研究基础上,通过动物模型和体外研究确定在COPD病理过程中β2-AAbs的变化及其与疾病进展的关系,阐明β2-AAbs对COPD气道重构的影响及其信号通路相关分子机制,同时采用小样本临床研究,观察β2-AAbs水平不同的患者对不同临床治疗的反应,此研究将丰富对COPD炎症反应的认识,并为COPD个体化治疗提供实验依据。
中文关键词: β2肾上腺素受体;自身抗体;慢性阻塞性肺疾病;气道重构;分子机制
英文摘要: Chronic inflammation and airway remodeling are important basis in the airflow obstruction progression of chronic obstructive pulmonary disease (COPD). In recent years, with lymphoid follicle in the lung tissue and Anti-autoantigen antibodies in serum were detected in COPD patients, humoral immunity has been given more attention. In our current study, the anti-β2-adrenergic receptor autoantibodies (β2-AAbs) level was increased in the serum from COPD patients and related to clinical symptom aggravation. Furthermore, β2-AAbs level rose with increased time in the rats exposed to cigarette smoking. In vitro study, we found that β2-AAbs may have agonists-like effect . Based on our former work, this project will determine β2-AAbs changes in the pathogenesis of COPD and its relationship with disease progression, clarify the effect of β2-AAbs on airway remodeling and related molecular mechanism. Clinical treatment response in subgroups of COPD patients with different β2-AAbs level will be included also. This study will enrich the recognition of COPD inflammation, and provide the experimental basis for the individual treatment to COPD patients.
英文关键词: β2-adrenergic receptor;autoantibodies;COPD;airway remodeling;molecular mechanism