哮喘患儿外周血单个核细胞中NLRP3炎症小体及血清中IL-1β和IL-18表达变化及其意义
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摘要
目的:观察哮喘患儿外周血单个核细胞中NOD样受体热蛋白结构域相关蛋白3 (NLRP3)炎症小体表达水平及血清中下游因子白细胞介素1β(IL-1β)和白细胞介素18 (IL-18)水平变化,探讨其对患儿病情评估的意义。方法:176例哮喘患儿根据临床表现分为急性发作期组(n=91)、慢性持续期组(n=49)和缓解期组(n=36),同期从门诊体检中心选取健康儿童60名作为对照组,采用肺功能仪检查各组研究对象肺功能。采用实时荧光定量PCR法检测各组研究对象外周血单个核细胞中NLRP3、含有CARD结构域的凋亡相关斑点样蛋白(ASC)和含半胱氨酸的天冬氨酸蛋白水解酶1 (Caspase-1)mRNA表达水平,采用酶联免疫吸附(ELISA)实验检测各组研究对象血清中IL-1β和IL-18水平。结果:与对照组比较,急性发作期组、慢性持续期组和缓解期组哮喘患儿第1秒用力呼气容积占预计值百分比(FEV1%)和第1秒用力呼气容积所占肺活量比值(FEV1/FVC)均降低,且急性发作期组<慢性持续期组<缓解期组,组间比较差异有统计学意义(P<0.05);哮喘患儿外周血单个核细胞中NLRP3、ASC和Caspase-1mRNA表达水平及血清中IL-1β和IL-18水平均高于对照组(P<0.01);急性发作期组患儿外周血单个核细胞中NLRP3、ASC和Caspase-1mRNA表达水平及血清中IL-1β和IL-18水平高于慢性持续期组和缓解期组(P<0.05),且慢性持续期组患儿高于缓解期组(P<0.05)。Pearson相关分析,哮喘患儿外周血单个核细胞中NLRP3 mRNA表达水平与ASC、Caspase-1mRNA表达水平和血清中IL-1β、IL-18水平均呈正相关关系(P<0.05),而与FEV1%和FEV1/FVC呈负相关关系(P<0.05);ASC mRNA表达水平与Caspase-1 mRNA表达水平和血清中IL-1β、IL-18水平呈正相关(P<0.05),而与FEV1%和FEV1/FVC呈负相关关系(P<0.05);Caspase-1mRNA表达水平与血清中IL-1β和IL-18水平呈正相关关系(P<0.05),而与FEV1%和FEV1/FVC呈负相关关系(P<0.05);血清中IL-1β水平与FEV1%和FEV1/FVC呈负相关关系(P<0.05);IL-18水平与FEV1%和FEV1/FVC呈负相关关系(P<0.05)。结论:哮喘患儿外周血NLRP3炎症小体及下游因子IL-1β和IL-18水平升高,且与哮喘患儿的临床分期有关,NLRP3炎症小体通路可能促进了儿童哮喘的发病过程。
Objective:To investigate the changes of expressions of NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome in the peripheral blood mononuclear cells and downstream factors interleukin-1β(IL-1β)and interleukin-18(IL-18)in serum in the children with asthma,and to explore their significances on assessing the condition of the children.Methods:A total of 176 cases of children with asthma were divided into acute exacerbation group(n=91),chronic persistent group(n=49)and clinical remission group(n=36)according to the clinical manifestation.During the same period,60 healthy children were selected from the outpatient physical examination center as control group.The pulmonary function of children was checked with lung function instrument.The expression levels of NLRP3,apoptosis-associated speck-like protein containing a CARD(ASC)and cysteinyl aspartate-specific proteinase-1(Caspase-1)mRNA in peripheral blood mononuclear cells of the subjects in various groups were detected by using real-time quantitative PCR.The serum levels of IL-1βand IL-18 of the subjects in various groups were detected by using enzyme-linked immunosorbent assay(ELISA).Results:Compared with control group,the forced expiratory volume in 1 second percentage of predicted value(FEV1%)and fixed ratio of forced expiratory volume in the first second/forced vital capacity(FEV1/FVC)of the children in acute exacerbation,chronic persistent and clinical remission groups were decreased(P<0.05);acute exacerbation group
Objective:To investigate the changes of expressions of NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome in the peripheral blood mononuclear cells and downstream factors interleukin-1β(IL-1β)and interleukin-18(IL-18)in serum in the children with asthma,and to explore their significances on assessing the condition of the children.Methods:A total of 176 cases of children with asthma were divided into acute exacerbation group(n=91),chronic persistent group(n=49)and clinical remission group(n=36)according to the clinical manifestation.During the same period,60 healthy children were selected from the outpatient physical examination center as control group.The pulmonary function of children was checked with lung function instrument.The expression levels of NLRP3,apoptosis-associated speck-like protein containing a CARD(ASC)and cysteinyl aspartate-specific proteinase-1(Caspase-1)mRNA in peripheral blood mononuclear cells of the subjects in various groups were detected by using real-time quantitative PCR.The serum levels of IL-1βand IL-18 of the subjects in various groups were detected by using enzyme-linked immunosorbent assay(ELISA).Results:Compared with control group,the forced expiratory volume in 1 second percentage of predicted value(FEV1%)and fixed ratio of forced expiratory volume in the first second/forced vital capacity(FEV1/FVC)of the children in acute exacerbation,chronic persistent and clinical remission groups were decreased(P<0.05);acute exacerbation group
引文
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[3]钟林庆.NLRP12及其在疾病发生和发展中的作用[J].国际儿科学杂志,2018,45(1):13-16.
[4]沈剑箫,王玲,姜娜,等.对比剂激活NLRP3炎症体通路诱导肾小管上皮细胞凋亡[J].中华肾脏病杂志,2018,34(1):36-43.
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[7]白翠芬.脉冲振荡肺功能检查对哮喘儿童病情评估的价值及与血清指标的相关性分析[J].海南医学院学报,2016,22(10):1016-1019,1023.
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[9]李莉,丁俊丽,荣杰鑫,等.呼出气冷凝液中LTB4和CCL11水平与儿童哮喘分期的研究[J].中国现代医学杂志,2017,27(9):133-136.
[10]NEERINCX A H,VIJVERBERG S J H,BOS L D J,et al.Breathomics from exhaled volatile organic compounds in pediatric asthma[J].Pediatr Pulmonol,2017,52(12):1616-1627.
[11]GONG T,YANG Y,JIN T,et al.Orchestration of NLRP3inflammasome activation by ion fluxes[J].Trends Immunol,2018,39(5):393-406.
[12]SAYAN M,MOSSMAN B T.The NLRP3inflammasome in pathogenic particle and fibre-associated lung inflammation and diseases[J].Part Fibre Toxicol,2016,13(1):51-57.
[13]何岱昆,卲义如,申捷,等.NLRP3炎症小体参与光气致急性肺损伤的炎症反应[J].中华劳动卫生职业病杂志,2017,35(7):491-496.
[14]HUANG M Y,TU C E,WANG S C,et al.Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3inflammasome in microglia[J].BMCComplement Altern Med,2018,18(1):221-227.
[15]LIU Y,GAO X,MIAO Y,et al.NLRP3 regulates macrophage M2polarization through up-regulation of IL-4in asthma[J].Biochem J,2018,475(12):1995-2008.
[16]KIM B G,LEE P H,LEE S H,et al.Effect of TiO2nanoparticles on inflammasome-mediated airway inflammation and responsiveness[J].Allergy Asthma Immunol Res,2017,9(3):257-264.
[17]TSAI Y M,CHIANG K H,HUANG J Y,et al.Der f1induces pyroptosis in human bronchial epithelia via the NLRP3inflammasome[J].Int J Mol Med,2018,41(2):757-764.
[18]LEAL V N C,GENOV I R,MALLOZI M C,et al.Polymorphisms in inflammasome genes and risk of asthma in Brazilian children[J].Mol Immunol,2018,93:64-67.
[19]ROSSIOS C,PAVLIDIS S,HODA U,et al.Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma[J].J Allergy Clin Immunol,2018,141(2):560-570.
[20]CHOI Y J,SUH D I,SOHN M H,et al.Dyspnea perception during induced bronchoconstriction is complicated by the inhaled methacholine in children with clinical asthma[J].Allergy Asthma Immunol Res,2018,10(2):131-136.
[2]郑伟华,欧维琳.儿童哮喘病情监测和控制水平评估的相关检查方法[J].医学综述,2017,23(9):1786-1790.
[3]钟林庆.NLRP12及其在疾病发生和发展中的作用[J].国际儿科学杂志,2018,45(1):13-16.
[4]沈剑箫,王玲,姜娜,等.对比剂激活NLRP3炎症体通路诱导肾小管上皮细胞凋亡[J].中华肾脏病杂志,2018,34(1):36-43.
[5]YAO S T,GAO F,CHEN J L,et al.NLRP3is required for complement-mediated caspase-1 and IL-1beta activation in ICH[J].J Mol Neurosci,2017,61(3):385-395.
[6]中华医学会儿科学分会呼吸学组,《中华儿科杂志》编辑委员会.儿童支气管哮喘诊断与防治指南(2016年版)[J].中华儿科杂志,2016,54(3):167-181.
[7]白翠芬.脉冲振荡肺功能检查对哮喘儿童病情评估的价值及与血清指标的相关性分析[J].海南医学院学报,2016,22(10):1016-1019,1023.
[8]RUTMAN L,MIGITA R,SPENCER S,et al.Standardized asthma admission criteria reduce length of stay in a pediatric emergency department[J].Acad Emerg Med,2016,23(3):289-296.
[9]李莉,丁俊丽,荣杰鑫,等.呼出气冷凝液中LTB4和CCL11水平与儿童哮喘分期的研究[J].中国现代医学杂志,2017,27(9):133-136.
[10]NEERINCX A H,VIJVERBERG S J H,BOS L D J,et al.Breathomics from exhaled volatile organic compounds in pediatric asthma[J].Pediatr Pulmonol,2017,52(12):1616-1627.
[11]GONG T,YANG Y,JIN T,et al.Orchestration of NLRP3inflammasome activation by ion fluxes[J].Trends Immunol,2018,39(5):393-406.
[12]SAYAN M,MOSSMAN B T.The NLRP3inflammasome in pathogenic particle and fibre-associated lung inflammation and diseases[J].Part Fibre Toxicol,2016,13(1):51-57.
[13]何岱昆,卲义如,申捷,等.NLRP3炎症小体参与光气致急性肺损伤的炎症反应[J].中华劳动卫生职业病杂志,2017,35(7):491-496.
[14]HUANG M Y,TU C E,WANG S C,et al.Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3inflammasome in microglia[J].BMCComplement Altern Med,2018,18(1):221-227.
[15]LIU Y,GAO X,MIAO Y,et al.NLRP3 regulates macrophage M2polarization through up-regulation of IL-4in asthma[J].Biochem J,2018,475(12):1995-2008.
[16]KIM B G,LEE P H,LEE S H,et al.Effect of TiO2nanoparticles on inflammasome-mediated airway inflammation and responsiveness[J].Allergy Asthma Immunol Res,2017,9(3):257-264.
[17]TSAI Y M,CHIANG K H,HUANG J Y,et al.Der f1induces pyroptosis in human bronchial epithelia via the NLRP3inflammasome[J].Int J Mol Med,2018,41(2):757-764.
[18]LEAL V N C,GENOV I R,MALLOZI M C,et al.Polymorphisms in inflammasome genes and risk of asthma in Brazilian children[J].Mol Immunol,2018,93:64-67.
[19]ROSSIOS C,PAVLIDIS S,HODA U,et al.Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma[J].J Allergy Clin Immunol,2018,141(2):560-570.
[20]CHOI Y J,SUH D I,SOHN M H,et al.Dyspnea perception during induced bronchoconstriction is complicated by the inhaled methacholine in children with clinical asthma[J].Allergy Asthma Immunol Res,2018,10(2):131-136.