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CN116223818B - Dr3蛋白检测试剂在制备筛查aecopd的试剂盒的用途及筛查aecopd的试剂盒 - Google Patents

Dr3蛋白检测试剂在制备筛查aecopd的试剂盒的用途及筛查aecopd的试剂盒 Download PDF

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CN116223818B
CN116223818B CN202310516991.8A CN202310516991A CN116223818B CN 116223818 B CN116223818 B CN 116223818B CN 202310516991 A CN202310516991 A CN 202310516991A CN 116223818 B CN116223818 B CN 116223818B
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CN116223818A (zh
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王浩
高嘉艺
詹悦涓
郝南亚
文富强
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West China Hospital of Sichuan University
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Abstract

本发明提供了DR3蛋白检测试剂在制备筛查AECOPD的试剂盒的用途及筛查AECOPD的试剂盒,属于体外诊断试剂领域。本发明首次发现AECOPD患者血清中DR3蛋白表达水平显著高于普通COPD患者以及健康人群。本发明将检测DR3蛋白表达水平的试剂用于制备AECOPD筛查试剂盒,能够实现AECOPD的有效筛查,具有良好的临床应用前景。

Description

DR3蛋白检测试剂在制备筛查AECOPD的试剂盒的用途及筛查 AECOPD的试剂盒
技术领域
本发明属于体外诊断试剂领域,具体涉及DR3蛋白检测试剂在制备筛查AECOPD的试剂盒的用途及筛查AECOPD的试剂盒。
背景技术
慢性阻塞性肺疾病(Chronic obstructive pulmonary disease,COPD)是一种常见的肺部疾病,其特征是持续的呼吸道症状和气流受制,可进一步发展为肺心病和呼吸衰竭。COPD与有害气体及有害颗粒的异常炎症反应有关,致残率和病死率很高,全球40岁以上发病率已高达9%~10%,是全球范围内发病率和死亡率最高的疾病之一。
慢性阻塞性肺疾病急性加重期(Acute exacerbation of pulmonary disease,AECOPD)是COPD临床过程中的重要事件,COPD患者每年发生约0.5~3.5次的急性加重,频繁的慢性阻塞性肺疾病急性加重会导致肺功能出现恶化,因此AECOPD是COPD患者死亡的重要因素。我国2007年修订的《慢性阻塞性肺疾病诊治指南》中AECOPD是指患者出现超越日常状况的持续恶化,并需改变基础COPD的常规用药者,通常在疾病过程中,患者短期内咳嗽、咳痰、气短和(或)喘息加重,痰量增多,呈脓性或粘脓性,可伴发热等炎症明显加重的表现。AECOPD的治疗方法主要是延缓疾病进展,缓解症状,因此早诊断、早治疗对于AECOPD十分重要。但是,目前对AECOPD的定义和诊断均为临床症状的描述,缺乏量化指标,易造成漏诊和误诊。
随着分子生物学的不断发展,生物标志物作为一种定量指标用于疾病的诊断成为研究热点。近年来,多种生物标志物被发现与COPD的发生发展有关,如VEGF、IL-6、IL-8、TNF-α等。但是对于AECOPD缺乏特异性和灵敏度高,预测效能优异的生物标志物。死亡受体3(DR3)是肿瘤坏死因子超家族(TNFSF)的一员,与肿瘤坏死因子配体相关分子-1A(TL1A)形成受体-配体复合物,调节免疫、炎症、细胞的增殖与死亡,参与多种疾病的进程。目前尚未见研究证明DR3与AECOPD诊断之间有明确的关系。
发明内容
为了解决现有技术存在的问题,本发明提供了DR3蛋白检测试剂在制备筛查AECOPD的试剂盒的用途及筛查AECOPD的试剂盒。
本发明提供了检测DR3蛋白的试剂在制备慢性阻塞性肺疾病急性加重期筛查试剂盒中的用途。
进一步地,所述检测DR3蛋白的试剂为酶联免疫分析试剂。
进一步地,所述检测DR3蛋白的试剂为western blot试剂。
进一步地,所述检测DR3蛋白的试剂为蛋白芯片检测方法用试剂。
进一步地,所述检测DR3蛋白的试剂为检测人血清中DR3蛋白的试剂。
本发明还提供了一种慢性阻塞性肺疾病急性加重期筛查试剂盒,它包括检测DR3蛋白的试剂。
进一步地,所述检测DR3蛋白的试剂为酶联免疫分析试剂。
进一步地,所述检测DR3蛋白的试剂为western blot试剂。
进一步地,所述检测DR3蛋白的试剂为蛋白芯片检测方法用试剂。
进一步地,所述检测DR3蛋白的试剂为检测人血清中DR3蛋白的试剂。
本发明的关键在于确定了待检测者血清中DR3蛋白表达水平与是否患有AECOPD显著相关,与普通COPD患者和健康人相比,DR3蛋白表达水平高则患AECOPD风险高,因此可以通过检测待检测者血清中DR3蛋白表达水平对其是否患有AECOPD进行筛查。至于具体检测血清中DR3蛋白表达水平的手段,可以采用现有技术公开的各种手段进行,不仅仅限于本发明实施例中使用的方法。任何能够检测血清中DR3蛋白表达水平的方法均可用于本发明。
与现有技术相比,本发明的有益效果为:
本发明研究发现DR3蛋白表达水平与AECOPD患者特异性相关,AECOPD患者血清中DR3蛋白表达水平显著高于普通COPD患者和健康人。因此,通过检测患者血清中DR3蛋白表达水平,可以对AECOPD进行筛查。若DR3蛋白表达水平高(相对于健康人和COPD患者),则患AECOPD的风险高,若DR3蛋白表达水平低,则患AECOPD的风险低。血清中DR3蛋白表达水平可用于临床AECOPD的诊断或辅助诊断,为患者相关的治疗措施或者决策提供有效的依据,临床应用前景良好。
显然,根据本发明的上述内容,按照本领域的普通技术知识和惯用手段,在不脱离本发明上述基本技术思想前提下,还可以做出其它多种形式的修改、替换或变更。
以下通过实施例形式的具体实施方式,对本发明的上述内容再作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基于本发明上述内容所实现的技术均属于本发明的范围。
附图说明
图1为COPD患者、AECOPD患者和健康志愿者血清中DR3蛋白的表达水平。
图2为COPD患者和AECOPD患者血清中DR3蛋白的表达水平的ROC分析。
图3为健康志愿者和AECOPD患者血清中DR3蛋白的表达水平的ROC分析。
具体实施方式
本发明具体实施方式中使用的原料、设备均为已知产品,通过购买市售产品获得。
实施例1、血清中DR3与AECOPD的关系
1、患者人群
华西医院门诊稳定型COPD患者112例,住院科急性加重(AECOPD)患者109例,69名健康志愿者。稳定型COPD患者和健康志愿者采用美国胸科学会指南采用的标准方法进行标准肺功能测试。慢性阻塞性肺病的诊断基于全球慢性阻塞性肺疾病倡议(GOLD)标准:(a)使用支气管扩张剂β/FVC<-激动剂(200 mg沙丁胺醇)后,(b)强迫肺活量(FVC)或FEV1<增加12%或200 mL。
2、样本检测
受试者肘静脉取空腹静脉血,以4°C,3000rpm直接离心10分钟,取上层血清。然后,将血清-80°C保存至分析,检测血清中DR3蛋白表达水平。采用Human Luminex® DiscoveryAssay(LXSAHM),在Bio-Plex 200检测平台(Bio-Rad,加利福尼亚,美国)上,根据制造商的说明进行检测,检测使用的试剂为抗人DR3抗体包被的磁珠,生物素标记的二抗,显色底物等,均可通过购买得到。DR3检测下限为58.6pg/mL。进行测量的操作者不知道受试者的临床信息。
3、结果数据
COPD患者、AECOPD患者和健康志愿者血清中DR3蛋白的表达水平如表1和图1所示。将3组DR3蛋白的表达水平数据进行比较,结果如表2所示。COPD患者和AECOPD患者ROC分析结果如图2、表3所示。健康志愿者与AECOPD患者的ROC分析结果如图3、表4所示。
表1.COPD、AECOPD患者和健康志愿者血清中DR3蛋白的表达水平
表2.COPD、AECOPD患者和健康志愿者血清中DR3蛋白表达水平的比较
表3.COPD患者和AECOPD患者ROC曲线分析结果
表4.健康志愿者与AECOPD患者的ROC分析结果
由上述数据可知:与COPD患者和健康志愿者相比,AECOPD患者血清中DR3蛋白表达水平显著提高,均有统计学差异。COPD患者与AECOPD患者ROC分析结果:AUC面积为0.829,最佳临界值为117.5950,特异性为60.7%,敏感性为95.4%。健康志愿者与AECOPD患者ROC分析结果:AUC面积为0.770,最佳临界值为240.5700,特异性为97.1%,敏感性为60.6%。
结果表明COPD患者与健康人血清中DR3表达水平差异较小,而AECOPD患者血清中DR3表达水平与COPD患者与健康人相比,差异很大。因此DR3蛋白可以特异性地将AECOPD患者和健康人、COPD患者区分开,并且用DR3蛋白作为标志物筛选AECOPD患者的特异性和灵敏度好。通过检测血清中DR3蛋白表达水平,能够达到对AECOPD筛查的目的。
综上,本发明研究发现DR3蛋白表达水平与AECOPD患者特异性相关,AECOPD患者血清中DR3蛋白表达水平显著高于普通COPD患者和健康人。因此,通过检测患者血清中DR3蛋白表达水平,可以对AECOPD进行筛查。若DR3蛋白表达水平高(相对于健康人和COPD患者),则患AECOPD的风险高,若DR3蛋白表达水平低,则患AECOPD的风险低。血清中DR3蛋白表达水平可用于临床AECOPD的诊断或辅助诊断,为患者相关的治疗措施或者决策提供有效的依据,临床应用前景良好。

Claims (5)

1.检测DR3蛋白的试剂在制备慢性阻塞性肺疾病急性加重期筛查试剂盒中的用途。
2.根据权利要求1所述的用途,其特征在于:所述检测DR3蛋白的试剂为酶联免疫分析试剂。
3.根据权利要求1所述的用途,其特征在于:所述检测DR3蛋白的试剂为western blot试剂。
4.根据权利要求1所述的用途,其特征在于:所述检测DR3蛋白的试剂为蛋白芯片检测方法用试剂。
5.根据权利要求1~4任一项所述的用途,其特征在于:所述检测DR3蛋白的试剂为检测人血清中DR3蛋白的试剂。
CN202310516991.8A 2023-05-09 2023-05-09 Dr3蛋白检测试剂在制备筛查aecopd的试剂盒的用途及筛查aecopd的试剂盒 Active CN116223818B (zh)

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