呼吸道合胞病毒毛细支气管炎患儿外周血心房钠尿肽和GATA3水平上调
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摘要
目的研究在不同程度毛细支气管炎患儿外周血中心房钠尿肽(ANP)信号变化和GATA结合蛋白3(GATA3)表达的关系,探讨ANP信号参与毛细支气管炎发病的可能机制。方法选取正常儿童20例、轻度毛细支气管炎患儿16例、中重度毛细支气管炎患儿14例。ELISA检测血浆中ANP及白细胞介素4 (IL-4)含量,实时荧光定量PCR检测外周血单个核细胞(PBMC)中钠尿肽受体A(NPRA)和GATA3 mRNA表达,Western blot法检测PBMC中NPRA、GATA3的蛋白水平。结果随疾病炎症程度升高,患儿血浆内ANP、IL-4水平明显升高,同时PBMC中NPRA和GATA3的mRNA及蛋白表达也随之升高。结论毛细支气管炎患儿外周血ANP、NPRA、IL-4和GATA3水平升高。
Objective To investigate the relationship between changes in atrial natriuretic peptide( ANP) signal and GATA3 expression in peripheral blood of children with bronchiolitis,and to explore the possible mechanism of ANP signal inthe pathogenesis of bronchiolitis. Methods 20 normal children,16 children with mild bronchiolitis,and 14 medium-severechildren were enrolled. ELISA was used to detect the level of ANP and interleukin-4( IL-4) in plasma. Real-time fluorescentquantitative PCR was performed to determine the mRNA expression of natriuretic peptide receptor A( NPRA) and GATA3 inperipheral blood mononuclear cells( PBMCs). Western blot analysis was used to determine the protein expression of NPRAand GATA3. Results As the degree of inflammation of bronchiolitis increases,the level of ANP and IL-4 in plasma increasedsignificantly,and the mRNA and protein expression of NPRA and GATA3 in PBMCs also increased. Conclusion The levelsof ANP,NPRA,IL-4 and GATA3 increased in peripheral blood of children with bronchiolitis.
Objective To investigate the relationship between changes in atrial natriuretic peptide( ANP) signal and GATA3 expression in peripheral blood of children with bronchiolitis,and to explore the possible mechanism of ANP signal inthe pathogenesis of bronchiolitis. Methods 20 normal children,16 children with mild bronchiolitis,and 14 medium-severechildren were enrolled. ELISA was used to detect the level of ANP and interleukin-4( IL-4) in plasma. Real-time fluorescentquantitative PCR was performed to determine the mRNA expression of natriuretic peptide receptor A( NPRA) and GATA3 inperipheral blood mononuclear cells( PBMCs). Western blot analysis was used to determine the protein expression of NPRAand GATA3. Results As the degree of inflammation of bronchiolitis increases,the level of ANP and IL-4 in plasma increasedsignificantly,and the mRNA and protein expression of NPRA and GATA3 in PBMCs also increased. Conclusion The levelsof ANP,NPRA,IL-4 and GATA3 increased in peripheral blood of children with bronchiolitis.
引文
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[15]Hu C,Li Z,Feng J,et al. Glucocorticoids modulate Th1 and Th2responses in asthmatic mouse models by inhibition of Notch1 signaling[J]. Int Arch Allergy Immunol,2018,175(1/2):44-52.
[16] Hoseini-Shahrestanak S,Bazargan N,Rahimian L,et al. Imbalancedexpression of Th2 and Treg cell-related parameters in peripheral bloodmononuclear cells in patients with allergic asthma[J]. Tanaffos,2018,17(1):1-12.
[17]刘位位,孙起翔,张景鸿,等.雾化吸入灭活草分枝杆菌对哮喘模型小鼠T-bet/GATA-3表达的影响[J].中国药理学通报,2018,34(8):1099-1104.
[18]白松,崔玉琳,柴若楠,等. CD4+T细胞通过分泌Th2型细胞因子介导RSV感染所诱发的气道炎症反应[J].中华微生物学和免疫学杂志,2017,37(10):747-752.
[19]Idzikowska K,Zielińska M. Midregional pro-atrial natriuretic peptide,animportant member of the natriuretic peptide family:potential role indiagnosis and prognosis of cardiovascular disease[J]. J Int Med Res,2018,46(8):3017-3029.
[20]Mohapatra S S,Lockey R F,Vesely D L,et al. Natriuretic peptidesand genesis of asthma:an emerging paradigm?[J]. J Allergy ClinImmunol,2004,114(3):520-526.
[21] Khoury E E,Kinaneh S,Aronson D,et al. Natriuretic peptidessystem in the pulmonary tissue of rats with heart failure:potentialinvolvement in lung edema and inflammation[J]. Oncotarget,2018,9(31):21715-21730.
[22]高远,曾锦荣,马礼兵,等.心房钠尿肽信号通路在小鼠支气管哮喘发病中的作用及其机制[J].新乡医学院学报,2015,32(4):291-298.
[23]马礼兵,高远,孙亚冰,等.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[J].武汉大学学报(医学版),2016,37(3):371-376.
[24]余园园,曾锦荣,孙亚冰,等.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[J].中南大学学报(医学版),2016,41(7):684-690.
[25]Ma L,Xiang X. Atrial natriuretic peptide/natriuretic peptide receptor A(ANP/NPRA)signaling pathway:a potential therapeutic target forallergic asthma[J]. Med Hypotheses,2011,77(5):832-833.
[2]Shrestha B,You D,Saravia J,et al. IL-4Rαon dendritic cells inneonates and Th2 immunopathology in respiratory syncytialvirus infection[J]. J Leukoc Biol,2017,102(1):153-161.
[3]刘良宵,吴福玲,张雪静,等.γ分泌酶抑制剂MW167致呼吸道合胞病毒毛细支气管炎患儿外周血单个核细胞中GATA3降低[J].细胞与分子免疫学杂志,2017,33(8):1035-1039.
[4]Zhang J,Li M,Yang Y,et al. NPR-A:A therapeutic target ininflammation and cancer[J]. Crit Rev Eukaryot Gene Expr,2015,25(1):41-46.
[5] Silberbach M,Roberts C T Jr. Natriuretic peptide signalling:molecularand cellular pathways to growth regulation[J]. Cell Signal,2001,13(4):221-231.
[6] Ma L,Zeng J,Mo B,et al. ANP/NPRA signaling preferentiallymediates Th2 responses in favor of pathological processes during thecourse of acute allergic asthma[J]. Int J Clin Exp Med,2015,8(4):5121-5128.
[7]胡亚美,江载芳,申昆玲,等.诸福棠实用儿科. 8版[M].北京:人民卫生出版社,2015:1276-1277.
[8]《中华儿科杂志》编辑委员会,中华医学会儿科学分会呼吸学组.毛细支气管炎诊断、治疗与预防专家共识(2014年版)[J].中华儿科杂志,2015,53(3):168-171.
[9]Feng S,Zeng D,Zheng J,et al. microRNAs:Mediators and therapeutictargets to airway hyper reactivity after respiratory syncytial virusinfection[J/OL]. Front Microbiol,2018,9:2177. DOI:10. 3389/fmicb. 2018. 02177. e Collection 2018.
[10]Russell C D,Unger S A,Walton M,et al. The human immuneresponse to respiratory syncytial virus infection[J]. Clin MicrobiolRev,2017,30(2):481-502.
[11] Vargas J E,de Souza A P,Porto B N,et al. Immunomodulatorplasmid projected by systems biology as a candidate for the development ofadjunctive therapy for respiratory syncytial virus infection[J]. MedHypotheses,2016,88:86-90.
[12] Zhang M,Lu Y,Zhang X,et al. Interleukin-4 polymorphism isassociated with severity of respiratory syncytial virus infection[J].J Paediatr Child Health,2016,52(1):25-29.
[13]Caminati M,Pham D L,Bagnasco D,et al. Type 2 immunity inasthma[J/OL]. World Allergy Organ J,2018,11(1):13.DOI:10. 1186/s40413-018-0192-5. e Collection 2018.
[14] Fedele G,Schiavoni I,Nenna R,et al. Analysis of the immuneresponse in infants hospitalized with viral bronchiolitis shows differentTh1/Th2 profiles associated with respiratory syncytial virus andhuman rhinovirus[J]. Pediatr Allergy Immunol,2018,29(5):555-557.
[15]Hu C,Li Z,Feng J,et al. Glucocorticoids modulate Th1 and Th2responses in asthmatic mouse models by inhibition of Notch1 signaling[J]. Int Arch Allergy Immunol,2018,175(1/2):44-52.
[16] Hoseini-Shahrestanak S,Bazargan N,Rahimian L,et al. Imbalancedexpression of Th2 and Treg cell-related parameters in peripheral bloodmononuclear cells in patients with allergic asthma[J]. Tanaffos,2018,17(1):1-12.
[17]刘位位,孙起翔,张景鸿,等.雾化吸入灭活草分枝杆菌对哮喘模型小鼠T-bet/GATA-3表达的影响[J].中国药理学通报,2018,34(8):1099-1104.
[18]白松,崔玉琳,柴若楠,等. CD4+T细胞通过分泌Th2型细胞因子介导RSV感染所诱发的气道炎症反应[J].中华微生物学和免疫学杂志,2017,37(10):747-752.
[19]Idzikowska K,Zielińska M. Midregional pro-atrial natriuretic peptide,animportant member of the natriuretic peptide family:potential role indiagnosis and prognosis of cardiovascular disease[J]. J Int Med Res,2018,46(8):3017-3029.
[20]Mohapatra S S,Lockey R F,Vesely D L,et al. Natriuretic peptidesand genesis of asthma:an emerging paradigm?[J]. J Allergy ClinImmunol,2004,114(3):520-526.
[21] Khoury E E,Kinaneh S,Aronson D,et al. Natriuretic peptidessystem in the pulmonary tissue of rats with heart failure:potentialinvolvement in lung edema and inflammation[J]. Oncotarget,2018,9(31):21715-21730.
[22]高远,曾锦荣,马礼兵,等.心房钠尿肽信号通路在小鼠支气管哮喘发病中的作用及其机制[J].新乡医学院学报,2015,32(4):291-298.
[23]马礼兵,高远,孙亚冰,等.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[J].武汉大学学报(医学版),2016,37(3):371-376.
[24]余园园,曾锦荣,孙亚冰,等.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[J].中南大学学报(医学版),2016,41(7):684-690.
[25]Ma L,Xiang X. Atrial natriuretic peptide/natriuretic peptide receptor A(ANP/NPRA)signaling pathway:a potential therapeutic target forallergic asthma[J]. Med Hypotheses,2011,77(5):832-833.