【作者】 王雯；

【作者基本信息】 新疆医科大学 ， 呼吸内科， 2003， 博士

【摘要】 支气管哮喘（哮喘）为Ⅰ型超敏性疾病，具有明显的个体差异，一般只有少数过敏体质的人才会发生。过敏体质与特应性（atopy）相关，亦与遗传有密切关系，有明显的家族聚集性，50％特应性患者的子代都患有特应性疾病，但所表现的症状即使在同一家族中也可不同。随着分子生物学与分子免疫学研究的不断深入，对参与哮喘在内的Ⅰ型超敏反应的IgE抗体、各种炎症细胞以及血小板活化因子（PAF）为代表的化学递质或细胞因子有了更新的理解。许多研究结果提示，哮喘除与上述因素以及自律神经异常、环境因素等有关外，遗传因素在其发病中起着举足轻重的作用。目前公认哮喘是一种具有多基因遗传倾向的疾病。我们在详细询问病史并进行肺功能检查的同时检测了新疆和田地区212例维吾尔族人群血样中的S-ECP、血清总IgE和吸入性变应原的特异性IgE抗体（Phadiatop）水平，以探讨新疆维吾尔族人群血清总IgE、特异性IgE及ECP与支气管哮喘发病的关系。同时，应用多聚酶链式反应—限制性片段长度多态性（PCR-RFLP）及等位基因特异性PCR（ASP）等现代分子生物学方法，对目前已知的可能涉及哮喘发病的β₂-AR16和27位点基因多态性、IL-4启动子区-589（C/T）位点基因多态性进行检测及其与总IgE的关系进行分析，旨在了解β₂-AR和IL-4二者的基因多态性与新疆维吾尔族人群哮喘的关联情况，从分子水平探索遗传因素在新疆维吾尔族人群哮喘发病中的作用。 一、血清总IgE、特异性IgE及ECP水平与维吾尔族人群支气管哮喘的关系 研究苔景和目的 哮喘是由多种炎症细胞及细胞因子（CKS）共同参与而形成的气道慢性变态反应性炎症。而嗜酸细胞己被公认是变态反应性疾病的标志。在变态反应和慢性炎症中起着重要作用。嗜酸细胞亦有免疫调节功能，在几个方面修饰T、B淋巴细胞、肥大细胞和中性粒细胞等的活性。此外，它在组织修复、重建和抗原的表达中亦起着重要作用。在嗜酸细胞释放的颗粒蛋白中，嗜酸细胞阳离于蛋白（ECP）和主要碱性蛋白（MBP）的毒性作用最强，而其中以ECP 更加明显，ECP被普遍认为是炎性反应标志，反映了嗜酸细胞的活化程度。测定病人血清、痰液及支气管肺泡灌洗液（BALF）中的ECP水平，可以判定哮喘炎症的严重程度及预后，预测疾病的发作，直接监测和指导抗炎治疗。为此，我们在详细询问病史并进行肺功能检查的同时检测了新疆和田地区维吾尔族人群血样中的 S干CP、血情总屹E和吸入性变应原的特异性lgE抗体ohadiatop)水平，以探讨新疆维吾尔族人群血清总IgE、特异性IgE及ECP与支气管哮喘发病的关系。 方法 作者于 2002年 3月在新疆和田地区共调查了 ZIZ例 18～72岁维吾尔族人（哮喘患者123例，正常对照89例），详细询问病史，采集血样并进行肺功能检查。根据临床特点、肺功能（FEVl占预计值％）和所需药物情况将患者分为间歇发作门 例)、轻度门 例)、中度（3例）、重度门 例)四个组，平均年龄38．35士9I7 岁。健康成年人89名，平均年龄3 8．12土8．23岁（18－71岁卜作为正常对照组。均采用真空S盯管采集和处理血清。血清肛P、皿清总lgE和吸入性变应原的特异性IgE抗体卯hadiatop）水平测定（血样）均在新疆医科大学变态反应检验中心（新疆医科大学第一附属医院耳鼻喉科）由固定资深专业测试人员进行测定，应用Un汇AP 00全自动体外变应原检测系统（SWEDEN PHARMACIA Un汇AP SystemS）检测，操作按说明进行，定量测定血清ECP、血清总IgE，同时对吸入性变应原的特异性IgE — —2一抗体（PhadiatoP）水平进行定性测定。测定所用试剂均由瑞典法玛西亚公司（PHARMACIA UniCAP，SWEDEN）提供。 结果 S正CP与哮喘的症状评分k SCOreX总 IgE和肺功能厌EVI和PEF)高度相关仪＜0乃1卜在哮喘各组之间，SECP都有显著性差异(均有 P＜0．01卜 最高值出现在重度哮喘患者组(EC叫．ZIfl。12 11g／LX且血清 ECP水平与病情严重程度呈正相关关系O－0石3，P＜0刀1＼同时还发现，变态反应的出现也与SICP值增高有关，IgE与SICP呈高度正相关关系…－o61，P＜0．01X｝＊CP值也都与哮喘发作的自觉症状和通过检查所得的客观体征具有高度相关性，ECP与PEF之间存在负相关关系O—0．67，P＜0刀5卜 以上结果表明，SICP和 lgE二者及其相互关系主要取决于嗜酸粒细胞激活程度和分泌蛋白的能力，它们能反映哮喘气道炎症的活动情况，并可预示哮喘发作的严重程度。 二、pZ－肾上腺素能受体基因多态性与新瞩锥吾尔族人群支气管哮喘及其临床表型的关系 研究背景和目的 pZ肾上腺素能受体（pZ－AR）基因与哮喘的关系一直受到广泛的重视。编码人02叭x的基困定位于染色体sq“”卫区，己有几个多态性位点被发现，其中编码区第16和27位氨基酸的变异已在体外实验中被证实其可以改变BZ人R的功能，是近年来国际上研究哮喘易感性及疾病调节基因的重要候选基因之一。我们以新?更多还原

【Abstract】 I Association between serum measurements of ECPx T-IgE and S-IgE with bronchial asthma in the Uygur populationBackground The accumulating knowledge during recent years has clearly indicated that one important cause of bronchial asthma is a kind of allergic and chronic inflanimation of the airway. In most instances the histopathology of this inflammation is characterized by the presence of an increased number of eosinophilic granulocytes. In particular, this seems to be true in the allergic type of asthma. Other causes of asthma way, in addition, involve other inflammatory cells such as the neutrophil. The role played by the eosinopb.il in the lung of the asthmatic patient is still not entirely clear. Although some data would indicate that these may be seperative in the process of epithelial shedding, either by a cytotoxic mechanism directed against the epithelial cells by the disruption of the structures necessary for the cells together. Other possibilities include a role in bronchoconstriction due to the production of leukotrienes and platelet-activating factor and the induction of glandular hypersecretion by ECP. Instrument in defining a role of the eosinophil in asthma have been studies employing broncho-alveolar lavage and biopsies of asthmatic subjects. Biopsy studies have shown the presence of activated eosinophils in the asthmatic lung and the disappearance of these cells after successfultreatment of asthma with inhaled corticosteroids. Similarly, lavage studies have shown a correlation between eosinophil numbers and ECP levels in the broncho-alveolar lavage on the one hand and the severity of asthma on the other. In addition, the studies showed a reduction in these variables by successful treatment. It should be emphasized that ECP levels were the only variables measured that, in these studies, consistently change is parallel with clinical improvement.The clinical management of asthma includes the monitoring of lung function and the anamnestic monitoring of the activity of daily living .It is well agreed that these measures are very often insufficient and do not accurately reflect, the underlying process of asthma, i.e. the extent of the inflammatory process. This is probably of the greatest importance, since it is well established that it may even be dangerous to treat the patients with symptomatic medication exclusively without controlling the underlying inflammayory process. The problem, however, is how to reflect accurately the inflammatory process of the asthmatic lung. Commonly used indicators of inflammatory activity such as blood ESR and acute-phase reactants in plasma are not altered in asthma.For some years we have been developing and testing the concept that the measurement of specific markers of various inflammatory activity in the body more sensitively than those tests commonly available today, and that such measurement would also provide unique information as to the underlying pathophysiological process of the disease. Until now we have developed assays specifically to reflect neutrophil activity [i.e. myeloperoxidase （MPO） and lactoferrin], eosinophil activity [i.e.ECP, eosinophil protein /eosinophil-derived neurotoxin （EPX/EDN）], eosinophil peroxidase （EPO）], and macrophage activity （i.e. lysozyme）. These assays could be supplemented by tryptase specifically to reflect mast cell activity.Objective To explore serum ECP, T-IgE and S-IgE levels of Xinjiang-10-Uygur population, to study the correalation and their clinical significance in asthmatic patients in different degrees, and to elucidate the role of ECP and IgE in the pathogenesis of bronchial asthma.Methods 123 Uyger asthmatics and 89 normal healthy controls with the same ethnic nearby Xinjiang Hetian region were investigated. The serum ECP and total IgE and specific aeroallergen were detected using a pharmacia UniCAP 100 type instrument, pulmonary ventilatory function assessed by FEV₁ and PEF.Results The positive rate of specific IgE antibody in asthmatics was 17.89%（22/123）. The inc更多还原