Zhang Y L, Zhao J, Zhao Y R, Zheng Y M, Guan L, Mao L J, Li S Q, Zhao J Y
Research Center of Occupational Medicine, Peking University Third Hospital, Beijing 100191, China.
Institute of Pharmacology and Toxicology Academy of Military Medical Science, Beijing 100850, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2020 Aug 20;38(8):566-569. doi: 10.3760/cma.j.issn.cn121094-20190927-00408.
To explore the role of extracellular histones in the pathogenesis of coal worker's pneumoconiosis (CWP) , the relationship of extracellular histones in plasma with pulmonary fibrosis caused by coal mine dust was analyzed, and the stimulating effect of extracellular histones on fibroblast proliferation was studied. In May 2019, a total of 220 coal mine dust exposure workers (including coal miners and CWP patients) who visited the occupational disease outpatient department of Peking University Third Hospital from 2012 to 2015 were enrolled in the study. According to the classification of small opacity profusion (SOP) in chest radiograph for pneumoconiosis diagnosis (category 0, 1, 2, 3) , 61 coal miners were in category 0 SOP, 65 coal miners were in category 1 SOP, 56 coal miners were in category 2 SOP and 38 coal miners were in category 3 SOP. The plasma levels of extracellular histone H4 and platelet-derived growth factor (PDGF) were measured by enzyme-linked immunosorbent assay (ELISA) kit. The stimulating effects of CWP patients' plasma and calf thymus histones (CTHs) on fibroblast and the antagonizing effect of anti-H4 antibody were investigated by fibroblast proliferation experiment in vitro. Among the study subjects, there were 195 males (88.6%, 195/220) and 25 females (11.4%, 25/220) , age (55.1±7.2) years, coal mine dust exposure time (16.3±4.4) years. The plasma concentrations of histone H4 in the coal miners with category 0, 1, 2 and 3 SOP were (3.92±1.75) 、(9.84±4.17) 、(14.35±5.52) and (17.83±7.69) μg/ml, respectively. There were significant differences among the four groups (<0.01) . The plasma level of histone H4 was positively correlated with the plasma level of PDGF in the coal miners (=0.769, <0.01) . Compared with healthy control plasma group, the cell proliferation percentages of patients' plasma group (272%±87%) and CTH group (283%±84%) were significantly increased (<0.05) . Compared with patients' plasma group, the cell proliferation percentage of patients' plasma+anti-H4 antibody group (185%±66%) was significantly decreased (<0.05) . Compared with CTH group, the cell proliferation percentage of CTH+anti-H4 antibody group (167%±59%) was significantly decreased (<0.05) . Extracellular histones in plasma are associated with pulmonary fibrosis in patients with CWP. Studies in vitro have shown that extracellular histones can promote proliferation of pulmonary fibroblasts. It is suggested that extracellular histones can be important biomarkers for pulmonary fibrosis caused by coal mine dust.
为探讨细胞外组蛋白在煤工尘肺（CWP）发病机制中的作用，分析血浆中细胞外组蛋白与煤矿粉尘所致肺纤维化的关系，并研究细胞外组蛋白对成纤维细胞增殖的刺激作用。2019年5月，选取2012年至2015年到北京大学第三医院职业病门诊就诊的220名煤矿粉尘接触工人（包括煤矿工人和CWP患者）纳入研究。根据尘肺病诊断时胸部X线片小阴影密集度（SOP）分类（0、1、2、3级），0级SOP的煤矿工人61名，1级SOP的煤矿工人65名，2级SOP的煤矿工人56名，3级SOP的煤矿工人38名。采用酶联免疫吸附测定（ELISA）试剂盒检测血浆中细胞外组蛋白H4和血小板衍生生长因子（PDGF）水平。通过体外成纤维细胞增殖实验，研究CWP患者血浆和小牛胸腺组蛋白（CTH）对成纤维细胞的刺激作用以及抗H4抗体的拮抗作用。研究对象中，男性195名（88.6%，195/220），女性25名（11.4%，25/220），年龄（55.1±7.2）岁，煤矿粉尘接触时间（16.3±4.4）年。0、1、2、3级SOP的煤矿工人血浆中组蛋白H4浓度分别为（3.92±1.75）、（9.84±4.17）、（14.35±5.52）和（17.83±7.69）μg/ml。四组间差异有统计学意义（<0.01）。煤矿工人血浆中组蛋白H4水平与PDGF水平呈正相关（=0.769，<0.01）。与健康对照血浆组相比，患者血浆组（272%±87%）和CTH组（283%±84%）的细胞增殖率显著升高（<0.05）。与患者血浆组相比，患者血浆+抗H4抗体组（185%±66%）的细胞增殖率显著降低（<0.05）。与CTH组相比，CTH+抗H4抗体组（167%±59%）的细胞增殖率显著降低（<0.05）。血浆中的细胞外组蛋白与CWP患者的肺纤维化有关。体外研究表明，细胞外组蛋白可促进肺成纤维细胞增殖。提示细胞外组蛋白可能是煤矿粉尘所致肺纤维化的重要生物标志物。
