【摘要】 目的通过对不同累积聚氯乙烯粉尘暴露浓度工人的血清蛋白量比较,探索疾病尚未发生前粉尘暴露的生物标志物,为预测尘肺病的风险概率及实施风险管理提供技术依据。方法采用高效液相色谱分离与ESI质谱鉴定联用的方法,对各组血清进行定性和半定量的鉴定,通过对各组间同一蛋白表达量的比较,以±2.0的差异倍数进行筛选,获得差异蛋白。通过Uniprot、GO、KEGG等软件对差异蛋白进行生物信息学分析,最终筛选理想的生物标志物。结果高暴露组与对照组相比,共计筛选出20种差异蛋白;对20种差异蛋白GO分析显示,差异蛋白主要参与细胞过程、生物调节、刺激反应以及新陈代谢等生物学过程;分子功能分析中显示其主要功能多与黏附、催化活性有关。两个暴露组均显示胰蛋白酶抑制剂重链1蛋白表达下调;CD163蛋白表达均呈上调,且具有一定的剂量-反应效应,低暴露组为2.6倍,高暴露组为3.1倍。结论聚氯乙烯粉尘暴露工人差异蛋白中,存在与炎症反应相关的蛋白,甚至出现与肿瘤相关的蛋白。提示在胸片或肺功能测定中未表现出临床异常的工人,其健康已受到影响,差异蛋白的筛选可对聚氯乙烯粉尘暴露的界限值探讨及尘肺病的预测预警有所帮助。更多还原

【Abstract】 Objective To explore the biomarkers of PVC dust exposure by comparison of the serum proteins of workers with different cumulative exposure doses,and provide the technical basis for predicting pneumoconiosis and implementing risk management. Methods High performance liquid chromatography separation( HPLC) combined electrospray ionization mass spectrometry( ESI-MS) was used to identify serum groups in both qualitative and semi-quantitative ways. The differential proteins were screened by ±2. 0 folds change. Bioinformatics were analyzed by Uniprot,GO,KEGG to screen the ideal biomarkers. Results Twenty kinds of differential proteins were selected by comparison between the high-level exposure group and control group. GO analysis showed the differential proteins mainly involved in cellular process,biological regulation,stimulation reaction,metabolism and other biological processes. Molecular functional analysis showed relevance between the adhesion and catalytic activity.Two exposure groups had the down-regulation of trypsin inhibitor heavy chain 1 protein,up-regulation of CD 163 proteins with a certain dose-response effect was found in two groups: 2. 6 fold in low-level exposure group and 3. 1 fold in high-level exposure group. Conclusion Inflammatory response related protein,even tumor related protein existed in the differential proteins of PVC dust exposed workers. It suggested that workers with no clinical abnormalities in X-ray diagnosis and pulmonary function testing may have certain health damage,and the differential proteins may have certain reference value in the dust exposure limits and pneumoconiosis prediction and early warning.更多还原