心房钠尿肽在过敏性哮喘气道炎症和气道高反应中的作用

Effects of Atrial Natriuretic Peptide on the Airway Inflammation and Hyperresponsiveness in the Allergic Asthma

目的:探讨外源性心房钠尿肽在过敏性哮喘气道炎症及气道高反应中的作用及其可能机制。方法:建立过敏性哮喘小鼠模型,观察心房钠尿肽的变化;同时利用肺功能、肺组织病理学、Western blot、ELISA方法检测干预心房钠尿肽信号后气道高反应性、炎症浸润、GATA3表达及IL-4等的变化。结果:与对照组比较,哮喘小鼠肺局部心房钠尿肽水平明显升高;而经鼻滴入外源性心房钠尿肽可缓解气道对乙酰甲胆碱的高反应性,但呈现出气道炎性渗出、黏液分泌及炎症细胞浸润加剧的效应;同时GATA3及IL-4等表达水平均升高;而利用拮抗剂预处理后,心房钠尿肽的上述效应可被明显逆转。结论:外源性心房钠尿肽可缓解气道高反应性但加剧过敏性哮喘的气道炎症,且可能具有不同的作用机制。

Objective：To explore the effects and possible mechanism of exogenous atrial natriuretic peptide involved in the airway inflammation and hyperresponsiveness of allergic asthma.Methods：By establishing mice model of allergic asthma,we detected the level of atrial natriuretic peptide,and meanwhile,pulmonary function test,lung histopathology,Western-blot,ELISA were applied to investigate the changes of airway hyperresponsiveness,inflammatory infiltration,expression of GATA3 protein,production of IL-4and so on after intervention of atrial natriuretic peptide signaling in vivo.Results：The level of atrial natriuretic peptide of BALF and lung homogenate from asthma group increased significantly,compared with those of control group.And administration of exogenous atrial natriuretic peptide by nasal drip could attenuate the airway hyperresponsive-ness in asthmatic mice,however unexpectedly,atrial natriuretic peptide aggravated inflammatory exudation,mucus secretion and infiltration of inflammatory cells.And expression of GATA3 and level of IL-4 were also promoted.Furthermore,the above effects were almost abrogated after pretreatment of atrial natriuretic peptide signal antagonist.Conclusion：Exogenous atrial natriuretic peptide can attenuate airway hyperresponsiveness while it may aggravate airway inflammation of allergic asthma,in which different mechanisms may play a role respectively.