煤工尘肺早期辅助诊断生物标志物研究
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摘要
目的探讨煤工尘肺(CWP)早期辅助诊断的生物标志物及其临床意义。方法采用立意抽样法,以69例男性煤矿粉尘作业工人为对照组,以67例男性CWP患者为CWP组。采集2组人群血清,以比色法测定其中丙二醛(MDA)及超氧化物歧化酶(SOD)水平,以酶联免疫吸附法测定白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平,以改良Ellman法测定乙酰胆碱酯酶(AChE)活力。采用Logistic回归模型分析CWP发病的危险因素,采用受试者工作特征(ROC)曲线分析CWP发病进程中的敏感指标。结果与对照组比较,CWP组人群血清中SOD活力下降(中位数:65.1 vs 59.2 kU/L,P<0.05),MDA、IL-6、TNF-α水平均升高(中位数:4.92 vs 6.68μmol/L,129.82 vs 163.18 ng/L,63.90 vs 70.93 ng/L,P<0.05)。Logistic回归分析结果显示,AChE是CWP的保护因素,年龄、慢性呼吸道症状、IL-6、MDA均是CWP的危险因素(P<0.05)。ROC曲线分析结果显示,IL-6和MDA均可作为煤矿粉尘作业工人CWP诊断的早期指标。结论血清中IL-6和MDA水平可作为CWP早期辅助诊断的生物标志物。
Objective To explore biomarkers for early auxiliary diagnosis of pneumoconiosis in coal workers(CWP) and its clinical significance. Methods Sixty-nine male coal miners exposed to dust were selected as control group, and sixty-seven CWP male patients were chosen as CWP group by purposive sampling method. Serum samples were collected from subjects of the two groups. The levels of malonaldehyde(MDA) and superoxide dismutase(SOD) were determined by colorimetric method. The enzyme-linked immunosorbent assay was used to measure the level of interleukin-6(IL-6) and tumor necrosis factor alpha(TNF-α). The acetylcholinesterase(AChE) activity was determined by modified Ellman method. The logistic regression model was used to analyze the risk factors of CWP. The receiver operating characteristic(ROC) curve was established to analyze the sensitive indicators in the pathogenesis of CWP. Results The serum SOD activity decreased(median: 65.1 vs 59.2 kU/L, P<0.05), and the MDA, IL-6 and TNF-α levels increased in the CWP group(median: 4.92 vs 6.68 μmol/L, 129.82 vs 163.18 ng/L, 63.90 vs 70.93 ng/L, P<0.05) compared with the control group. The logistic regression analysis results showed that AChE was the protective factor of CWP, while age, chronic respiratory symptoms, IL-6 and MDA were the risk factors of CWP(P<0.05). The ROC curve showed that IL-6 and MDA can be used as early indicators for the diagnosis of CWP in dust-exposed workers. Conclusion The serum IL-6 and MDA levels can be used as biomarkers for early auxiliary diagnosis of CWP.
Objective To explore biomarkers for early auxiliary diagnosis of pneumoconiosis in coal workers(CWP) and its clinical significance. Methods Sixty-nine male coal miners exposed to dust were selected as control group, and sixty-seven CWP male patients were chosen as CWP group by purposive sampling method. Serum samples were collected from subjects of the two groups. The levels of malonaldehyde(MDA) and superoxide dismutase(SOD) were determined by colorimetric method. The enzyme-linked immunosorbent assay was used to measure the level of interleukin-6(IL-6) and tumor necrosis factor alpha(TNF-α). The acetylcholinesterase(AChE) activity was determined by modified Ellman method. The logistic regression model was used to analyze the risk factors of CWP. The receiver operating characteristic(ROC) curve was established to analyze the sensitive indicators in the pathogenesis of CWP. Results The serum SOD activity decreased(median: 65.1 vs 59.2 kU/L, P<0.05), and the MDA, IL-6 and TNF-α levels increased in the CWP group(median: 4.92 vs 6.68 μmol/L, 129.82 vs 163.18 ng/L, 63.90 vs 70.93 ng/L, P<0.05) compared with the control group. The logistic regression analysis results showed that AChE was the protective factor of CWP, while age, chronic respiratory symptoms, IL-6 and MDA were the risk factors of CWP(P<0.05). The ROC curve showed that IL-6 and MDA can be used as early indicators for the diagnosis of CWP in dust-exposed workers. Conclusion The serum IL-6 and MDA levels can be used as biomarkers for early auxiliary diagnosis of CWP.
引文
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[14] 李娟,郝小惠,范雪云,等.尘肺患者血清肿瘤坏死因子、白细胞介素-6表达水平及意义[J].中国职业医学,2012,39(3):245-246.
[15] 高彬,郝长付,王永星,等.尘肺患者血清肿瘤坏死因子-α表达水平的Meta分析[J].卫生研究,2011,40(6):789-791.
[2] 李涛.新时期职业病防治形势分析及对策建议[J].中国职业医学,2018,45(5):537-542.
[3] 沈国安,刘瑾.尘肺发病机制研究进展[J].职业卫生与病伤,2002,17(1):32-40.
[4] 姚武,王治明,王绵珍,等. 煤工尘肺患者血清细胞因子及氧化损伤水平研究[J]. 四川大学学报(医学版),2005,36(4):510-512.
[5] 莫新,梁艳冰,陈志斌,等.重症肺炎患者血清胆碱酯酶含量变化及其与急性病生理学和长期健康评价Ⅱ评分、多器官功能障碍综合征评分的相关性研究[J].中华危重症医学杂志(电子版),2016,9(3):159-162.
[6] 殷晓明,殷兰芳,唐海沁.老年慢性阻塞性肺疾病急性加重患者血清前白蛋白和胆碱酯酶测定的意义[J].中华临床医师杂志(电子版),2012,6(8):2201-2202.
[7] 王素华,杜茂林,张翼翔,等.尘肺患者血中一氧化氮、丙二醛、超氧化物歧化酶浓度变化的研究[J].中国职业医学,2009,36(1):40-42.
[8] 王炳花,张美荣,张玉东.尘肺患者血清超氧化物歧化酶的检测分析[J].中国卫生产业,2012(27):136,138.
[9] LANG D, SCHOCKER H, HOCKERTZ S. Effects of crocidolite asbestos on human bronchoepithelial-dependent fibroblast stimulation in coculture: the role of IL-6 and GM-CSF[J]. Toxicology,2001,159(1):81-98.
[10] 姚三巧,吴卫东,卢遥,等.IL-1β、-6、-8、-10及干扰素-γ在煤工尘肺早期诊断中的应用[C]//中国毒理学会免疫毒理专业委员会.第六届中国毒理学会免疫毒理专业委员会换届及学术会议资料汇编.中国毒理学会免疫毒理专业委员会,2016:4.
[11] 郭菲菲,孙海霞,张志宇,等.煤工尘肺血清中TNF-α的表达及其早期筛检的作用研究[C]//中华预防医学会劳动卫生与职业病分会.第十三次全国劳动卫生与职业病学术会议论文汇编.中华预防医学会劳动卫生与职业病分会,2014:2.
[12] 余艳琴,郝金奇,姚三巧,等. TNF-α/TNFR/NF-κB通路对煤工尘肺患者肺泡巨噬细胞凋亡调控机制[J].中国职业医学,2017,44(3):303-308.
[13] 郭伟,王平,杨华敏,等.煤工尘肺患者血清和肺泡灌洗液中肿瘤坏死因子-α水平与肺功能关系研究[J].中国职业医学,2016,43(1):48-51.
[14] 李娟,郝小惠,范雪云,等.尘肺患者血清肿瘤坏死因子、白细胞介素-6表达水平及意义[J].中国职业医学,2012,39(3):245-246.
[15] 高彬,郝长付,王永星,等.尘肺患者血清肿瘤坏死因子-α表达水平的Meta分析[J].卫生研究,2011,40(6):789-791.