【作者】 张艳丽；

【导师】 栾斌； 贾天明；

【作者基本信息】 郑州大学 ， 儿科学， 2004， 硕士

【摘要】 背景与目的：支气管哮喘(Bronchial asthma BA以下简称哮喘)是全球范围内严重威胁公众健康的慢性疾病，是由肥大细胞、嗜酸性粒细胞(Eosinophil EOS)及T淋巴细胞等效应细胞分泌一系列炎症介质而诱发的气道慢性炎症。近几年随着免疫学和分子生物学的进展，对哮喘发病机制的研究由原来的分子水平进入基因水平，一些新的炎症介质如细胞因子成为研究的热点。细胞因子是细胞间相互作用的“信使”，是由活化的免疫细胞和基质细胞分泌的、介导和调节免疫反应的小分子多肽。白细胞介素-13(Interleukin-thirteen IL-13)主要是由活化的CD4~+辅助性T细胞(TH2)分泌的一种细胞因子，新近发现参与哮喘气道慢性炎症的形成。鳞状细胞癌抗原(Squamous cell carcinoma Antigen SccAg)是一种新型的肿瘤相关抗原，是半胱氨酸及丝氨酸蛋白酶的抑制剂。研究表明，IL-13所诱导的基因中SccAg表达最多，因此，推测SccAg在哮喘的发病中也起重要作用。联合检测IL-13、SccAg可能会对哮喘病情发展及转归的监测、诊断及治疗具有重要价值，此研究国内尚无人报道。 毛细支气管炎(以下简称毛支)是婴幼儿时期最常见的急性下呼吸道感染之一，流行病学调查发现，婴幼儿时期患过呼吸道合胞病毒(Respiratory syntheticvirus RSV)毛支的患儿约50％～70％可发生反复喘息，甚至哮喘。咳嗽变异性哮喘(Cough variant asthma CVA)是小儿慢性咳嗽的主要疾病之一，其唯一症状是慢性咳嗽而没有典型哮喘的喘息，易误诊、漏诊，严重危害小儿健康。两者与哮喘的关系至今不甚明了，因此从发病机制探讨它们之间的关系意义重大，而对于三者关系的研究国内外尚未见报道。 本实验中，我们采用酶联免疫吸附试验(Enzyme-linked immunosorbent assayEHSA)法检测32例哮喘患儿、25例CVA患儿、36例毛支患儿、40例肺炎患郑州大学刀I碎届硕日口与{胜毕州仑文嘟瑞患儿111睛协13、S毛入g淞F洲七和意义及l口:毛支、吻嗽变异幽中鱿能冷系的探讨儿及33例正常儿童血清IL一13、sccAg及免疫球蛋白E(l mmunoglobulin E IgE)水平，以观察哮喘患儿血清IL一13、SccAg水平变化和意义、并探讨哮喘与毛支、CVA的关系，从而避免毛支演变为哮喘及CVA的误诊、漏诊。 材料和方法:用ELISA法检测哮喘发作期患)七26例、缓解期32例，25例CVA患儿、36例毛支患儿、40例肺炎患儿均处于发作期，及33例正常儿童血清IL一13、SccAg及IgE水平，各组年龄、性别等方面经统计学处理差异无显著意义(尸>0.05)。采用SPSSn.0统计软包处理，结果以均数土标准差(万，、)，各组参数均符合正态分布，各组样本均数比较经方差齐性分析后采用t检验和F检验，回归采用直线回归，相关性采用直线相关分析，P<0.05有显著性差异。 结果:1.哮喘患儿发作期血清IL13(147.01土23.79)n幼、SceAg(3.01，0.37)n岁ml水平显著高于缓解期(86.08‘ 20.88)n幼、(2.46‘0.37)ng/ml及正常组(77.27“18.16)ng/l、(2.29“0.34)ng/ml(p<0.001)，但缓解期及正常组间无显著性差异(尸>.05);哮喘患儿发作期血清IgE(659.53‘70.51)KU几水平显著高于缓解期(414.62‘77.05)KU几，两组均显著高于正常组(151.67‘70.17)KU/L(p<0.001)，见附表1。 2.中、重度哮喘患儿血清IL一13(159.17‘21.96)n留l、SecAg(3.26士0·30)ng/ml及IgE(711.53，56.59)KU夕L水平显著高于轻度患儿(139.41，22.22)n幼:(2.84‘0.31)ng/ml、(627.03，58.61)KU/L(p<0.05)，见附表2。 3.肺炎组血清IL一13(80.74‘18.08)n幼、SeeAg(2.31‘0.35)ng/ml及IgE( 152.87，66.91)KU/L水平与正常组(77.27，18.16)n幼、(2.29士0.34)n留ml、(151.67，70.17)KU几相比无显性著差异(尸>0.05)，见附表3。 4.哮喘患儿血清IL一13(147.01，23.79)n幼、SeeAg(3.01士o·37)ng/ml、IgE(659.53“70.51)KU/L与CVA患儿(141.10，24.14)ng/l、(2.84‘0.39)ng/ml、(630.83，68.%)KU凡水平间无显著性差异(尸>0.05)，两者均显著高于毛支患儿(104.91，18.05)ng/l、(2.49‘0.36)n岁ml、(370.91‘69.26)KU/L(p<0.001)，见附表4。 5.毛支患儿血清IL一13(104.91士18.05)n幼、SeeAg(2.49‘0.36)ng/ml及IgE(370.91，69.26)KU/L水平显著高于肺炎组(80.74，18.08)ng/l、(2.31‘0.35)n留ml、(152.87‘66.91)KU/L(尸<0.05)，见附表5。荆十l大学么I域翩项士句e醉注毕业沦文嘟尚患儿血清113、放叱水平变化干呛义及J以升已支、喷魁瞬冲申l靛关系郎探讨 6.哮喘患儿发作期、缓解期血清IL一13、sccAg及IgE水平三者互呈正相关(r=0 .958，P<0.01;r二0.955，P<0.01;r二0.998，P<0.01)，(r=0.998，P<0.01:r=0.948，尸<0.01;:=0.945，尸<0.01)，见附表6。 结论:1.IL一13、sccAg可能在哮喘发病机制中起一定作用，联合检测血清IL一13及sccAg水平对哮喘病情发展及转归的监测、诊断及治疗具有重要价值。 2.毛支具有与哮喘相似的过敏反应特征，因此，临床上用抗过敏药物及刀受体兴奋剂治疗毛支具有合理性。 3.CVA与哮喘关系密切，CVA是典型哮喘的前驱表现。更多还原

【Abstract】 Background and objectives: Bronchial asthma (abbreviating asthma) is a chronic disease that seriously threaten human health over the world, it is a kind of chronic inflammation of airway, which is induced by a series of inflammation mediators, such as mast cells, eosinophils , T lymphocytes and so on. Recently, with the development of immunology and molecular biology, study of pathogenesis of asthma from molecule to.gene Some new inflammtion mediators become focus. Cytokine is a messenger of interaction of intercells, it is secreted by living immune cell and small molecule polypeptide of mediating and regulating immune reaction.Iterleukin-thirteen(IL-13) is a kind of cytokine, secreted by living CD"1" helping T cell(TH2), recently found involving in formation of chronic inflammation of airway in asthma. Squamous cell carcinoma Antigen(SccAg) is a new type of related tumor antegens, is cysteine and serine protease inhibitors, study indicate SccAg shows the highest expression all of genes induced by IL-13, therefore, it is supposed that SccAg may play some role in the pathogenesis of asthma. United measuring serum IL-13, SccAg concentration is useful for monitoring development and remission, diagnosis and theraphy, the study has not been reported until now in China.Bronchialitis is a kind of acute down respiratory infections, epidemicology indicate children who suffered Respiratory synthetic virus(RSV) bronchialitis during childhood, 50%~70% of them will occur recurrent wheeze, even asthma. Cough variant asthma(CVA) is a main kind of disease of chronic cough in children, onlysymptom is chronic cough out of classic wheeze of asthma, it is easy to disdiagnosis and omitting diagnosis, it threaten children health seriously. It is not clear of the relation among bronchialitis, CVA and asthma until now. So it is significant from pathogenesis to inquire the relation among them, the study has not been reported all over the world.In the experiment, we use enzyme-linked immunosorbent assay(ELISA) to measure serum IL-13, SccAg and immunoglobulin E(IgE) levels in 32 children with asthma, 25 children with CVA, 36 children with bronchialitis and 33 normal children, for knowing variances and significances of serum IL-13, SccAg in children with asthma and preliminary inquirement to relations among asthma, bronchialitis and CVA, to avoid bronchialitis becoming asthma, disdiagnosis and omitting diagnosis of CVA.Materials and Methods: Using ELISAto measure serum IL-13, SccAg and IgE levels of 26 children with asthma in acute phase, 32 children with asthma in remission phase, 25 children with CVA, 36 children with bronchialitis, 40 children with pneumonia and 33 normal children, age, sex and so on are not significant analyzed by statistics(P>0.05). Using SPSS 11.0 statistical software , mean and standand( x s) indicate results, every group parameters conform to normal distribution, sample averages of every group are analyzed after analysis of even variance, after that using t and F test, using linear regression, linear correlation analyse, P value less than 0.05 indicate statistical significance.Results: l.Serum IL-13(147.01 23.79)ng/l and SccAg(3.01 0.37)ng/ml concentration are significantly higher in acute phase of asthma than in period of remission(86.08 20.88)ng/l, (2.46 0.37)ng/ml (P<0.001), whereas period of remission and control group(77.27 18.16)ng/l, (2.29 0.34)ng/ml are not significantly different(P>0.05);.Serum IgE concentration in acute phase of asthma(659.53 70.51)KU/L are significantly higher than in period of remission(414.62 77.05)KU/L, furthermore, they are significantly higher than control group(151.67 70.17) KU/L (P<0.001), view in table 1.2. Serum IL-13(159.17 21.96)ng/l, SccAg(3.26 0.30)ng/ml andIgE(711.53 56.59)KU/L concentration in medium, serious asthma are significantly higher than light asthma(139.41 22.22)ng/l, (2.84 0.31)ng/ml, (627.03 58.61)KU/L (P<0.01),view in table 2.3. Serum IL-13(80.74 18.08)ng/l, SccAg(2.31 0.35更多还原