不同程度过敏性哮喘患者外周血ANP信号变化及其与哮喘发病的关系  

Serum levels of ANP signaling in different degree of allergic asthmatics and its role in the pathogenesis of allergic asthma

作　　者：余园园[1,2] 曾锦荣[1,2] 孙亚冰[1,2] 韦江红[1,2] 黄剑伟[1,2] 马礼兵[1,2] 

机构地区：[1]桂林医学院附属医院呼吸内科 [2]桂林医学院附属医院呼吸疾病研究所,广西桂林541001

出　　处：《中南大学学报（医学版）》2016年第7期684-690,共7页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(81360006;81560007);广西壮族自治区自然科学基金(2015GXNSFAA139106);广西医疗卫生适宜技术研究与开发项目(S201316-02)~~

摘　　要：目的:观察不同程度过敏性哮喘患者外周血心房钠尿肽(atrial natriuretic peptide,ANP)信号的变化,探讨其与哮喘程度的关系及ANP信号参与哮喘发病的可能机制。方法:共收集桂林医学院附属医院96例患者外周血标本,其中正常组23例、过敏性哮喘稳定组25例、轻度急性发作组21例、中度急性发作组27例。ELISA检测血清ANP及IFN-γ,IL-4的含量,RT-PCR及Western印迹分别检测利钠肽受体A(natriuretic peptide receptor A,NPA)及T盒21转录因子(T-box 21 transcription factor,T-bet),GATA结合蛋白3(GATA3 binding protein 3,GATA3)的mRNA与蛋白表达变化。结果:哮喘轻度发作组外周血ANP水平及单个核细胞(peripheral blood mononuclear cell,PBMC)中NPA的m RNA及蛋白表达水平均高于稳定组(P<0.05),中度发作组则高于轻度发作组(P<0.05);GATA3的表达及IL-4的水平在各组间变化趋势亦一致,即轻度发作组高于稳定组(P<0.05),中度发作组则高于轻度发作组(P<0.05)。而血清ANP水平随着哮喘严重程度加重而升高,与T-bet/GATA3和IFN-γ/IL-4值则呈负相关(r=–0.85,P<0.05;r=–0.88,P<0.05)。结论:外周血ANP信号水平随着过敏性哮喘严重程度加重而升高,提示与哮喘发病密切相关。ANP信号可能通过介导h 2型免疫应答优势化而参与过敏性哮喘发病。Objective： To investigate the relationship between the severity of allergic asthma and the levels of atrial natriuretic peptide （ANP）, and to analyze the potential role of ANP signaling in the pathogenesis of asthma. Methods： We recruited 96 subjects, including 23 healthy volunteers, 25 stable allergic asthmatics, 21 mild allergic asthmatics and 27 moderate allergic asthmatics, from the Affiliated Hospital of Guilin Medical University. ANP, IFN-7 and IL-4 levels in serum were detected by enzyme-linked immunosorbent assay （ELISA）, and the mRNA and protein expressions of natriuretic peptide receptor A （NPRA）, transcription factor T-bet and GATA3 were measured by RT-PCR and Western blot. Results： The levels of ANP in serum and the expressions of NPRA mRNA and protein in the peripheral blood mononuclear cell （PBMC） from the mild asthma group or the moderate group were elevated compared with those in the stable asthma group or the mild group, respectively （P〈0.05）. Consistently, expressions of GATA3 and levels of IL-4 showed the same tendency （P〈0.05）. In addition, levels of ANP in serum were positively correlated with the severity of asthma, whereas negatively correlated with the ratio of T-bet/GATA3 and IFN-3,/IL-4 （r=-0.85, P〈0.05; r=-0.88, P〈0.05, respectively）. Conclusion＂ Levels of ANP signaling in serum were significantly increased with the severity of allergic asthma, suggesting a close relation with the pathogenesis of asthma; ANP signaling may play a role in the pathogenesis of allergic asthma through inducing the Th2-type immune response.

关 键 词：过敏性哮喘 心房钠尿肽 外周血 TH1/TH2 细胞免疫 

分 类 号：R562.25[医药卫生—呼吸系统]