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中华肺部疾病杂志(电子版) ›› 2025, Vol. 18 ›› Issue (04) : 564 -569. doi: 10.3877/cma.j.issn.1674-6902.2025.04.012

论著

支气管肺泡灌洗液miR-125a-5p与矽肺患者疾病严重程度及肺功能相关性研究
罗玉1, 袁章安2,†(), 禹阳明2, 汪定军3, 熊忠林3, 蒋宁芳3   
  1. 1725000　安康，安康职业技术学院第二附属医院重症医学科
    2725000　安康，安康职业技术学院第二附属医院呼吸内科
    3725000　安康，安康市人民医院呼吸内科
  • 收稿日期:2025-04-14 出版日期:2025-08-25
  • 通信作者: 袁章安
  • 基金资助:
    陕西省药学会"医院药学高质量发展研究项目"(XM-2023-1-2-8)

Correlation research on miR-125a-5p in bronchoalveolar lavage fluid with disease severity and pulmonary function in patients with silicosis

Yu Luo1, Zhangan Yuan2,†(), Yangming Yu2, Dingjun Wang3, Zhonglin Xiong3, Ningfang Jiang3   

  1. 1Department of Critical Care Medicine, Ankang Vocational and Technical College Second Affiliated Hospital, Ankang 725000, China
    2Department of Respiratory Medicine, Ankang Vocational and Technical College Second Affiliated Hospital, Ankang 725000, China
    3Department of Respiratory Medicine, Ankang People′s Hospital, Ankang 725000, China
  • Received:2025-04-14 Published:2025-08-25
  • Corresponding author: Zhangan Yuan
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引用本文：

罗玉, 袁章安, 禹阳明, 汪定军, 熊忠林, 蒋宁芳. 支气管肺泡灌洗液miR-125a-5p与矽肺患者疾病严重程度及肺功能相关性研究[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(04): 564-569.

Yu Luo, Zhangan Yuan, Yangming Yu, Dingjun Wang, Zhonglin Xiong, Ningfang Jiang. Correlation research on miR-125a-5p in bronchoalveolar lavage fluid with disease severity and pulmonary function in patients with silicosis[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(04): 564-569.

目的

分析支气管肺泡灌洗液(bronchoalveolar lavage fluid, BALF)miR-125a-5p水平与矽肺患者疾病严重程度和肺功能的相关性。

方法

选择2019年3月至2024年4月我院收治的经支气管肺泡灌洗矽肺患者109例为对象，根据疾病严重程度分组，0期53例为对照组，Ⅰ~Ⅲ期56例为观察组。采用实时荧光定量聚合酶链式扩增分析BALF miR-125a-5p水平，比较两组肺功能、BALF细胞因子。

结果

观察组BALF miR-125a-5p水平3.26(2.25，3.82)高于对照组1.06(0.62，1.32)(Z＝－8.052，P<0.001)。多元Logistics回归分析显示，吸烟史(HR：4.395，95%CI：1.671~11.559，P＝0.003)及BALF miR-125a-5p水平(HR：47.848，95%CI：4.396~520.783，P<0.001)为患矽肺的危险因素，BALF miR-125a-5p水平变异存在聚集性(效应估算＝22.670，P＝0.029)，吸烟史对BALF miR-125a-5p水平固定效应有统计学意义(F＝158.993，P<0.001)。BALF miR-125a-5p水平对矽肺诊断受试者工作特性曲线下面积为0.947(95%CI：0.887~0.981)，BALF miR-125a-5p水平对矽肺的诊断灵敏性及特异性分别为89.29%、90.57%。观察组Ⅰ期31例(55.36%)、Ⅱ期16例(28.57%)、Ⅲ期9例(16.07%)。BALF miR-125a-5p水平Ⅰ期2.36(1.84，3.26)、Ⅱ期3.50(3.26，4.10)、Ⅲ期4.25(3.50，4.42)高于对照组1.06(0.62，1.32)(H＝70.774，P<0.001)；Ⅰ~Ⅲ期矽肺患者BALF miR-125a-5p逐期升高。矽肺患者BALF miR-125a-5p中位值3.26，BALF miR-125a-5p≥3.26患者肺活量(VC)(69.71±5.33)%、第1秒用力呼气容积(FEV1)(78.24±12.20)%、用力肺活量(FVC)(71.39±11.253)%、一氧化碳扩散容量(DLCO)(61.22±11.12)%低于BALF miR-125a-5p<3.26患者VC[(75.50±2.44)%，t＝5.161，P<0.001]、FEV1[(85.39±13.10)%，t＝2.115，P＝0.039]、FVC[(80.64±12.39)%，t＝2.928，P＝0.005]、DLCO[(72.19±14.82)%，t＝3.147，P＝0.003]。BALF miR-125a-5p≥3.26患者发生限制性呼吸机功能障碍概率大[26(89.66%)比11(40.74)，P<0.001]。Spearman秩相关性分析显示，矽肺患者BALF miR-125a-5p水平与白细胞介素(IL)-5、IL-6、IL-17A、肿瘤坏死因子α(TNF-α)、干扰素诱导蛋白10(IP-10)呈正相关(rs＝0.299~0.671，P<0.05)。

结论

BALF miR-125a-5p高水平与矽肺严重程度增加和肺功能降低相关。

关键词: 矽肺, 支气管肺泡灌洗液, miR-125a-5p, 疾病严重程度, 肺功能
Objective

To analyze the relationship between the level of miR-125a-5p in bronchoalveolar lavage fluid (BALF) and the severity of disease and lung function in silicosis patients.

Methods

A total of 109 patients with silicosis who underwent bronchoalveolar lavage and were admitted to our hospital from March 2019 to April 2024 were selected as the subjects. They were grouped according to the severity of the disease. 53 cases in stage 0 were the control group, and 56 cases in stages Ⅰ to Ⅲ were the observation group. The level of miR-125a-5p in BALF was analyzed by real-time fluorescence quantitative polymerase chain amplification, and the lung functions and BALF cytokines of the two groups were compared.

Results

The level of BALF miR-125a-5p in the observation group was significantly higher than that in the control group [3.26 (2.25, 3.82) vs. 1.06 (0.62, 1.32), Z=-8.052, P<0.001]. Multivariate Logistics regression analysis showed that combined smoking history and BALF miR-125a-5p level were independent risk factors for silicosis in workers, and the variation of BALF miR-125a-5p level between the observation group and the silicosis group was clustered (effect estimate=22.670, P=0.029), and the fixed effect of smoking history [HR: 4.395, 95%CI: 1.671~11.559, P=0.003] on BALF miR-125a-5p level[HR: 47.848, 95%CI: 4.396~520.783, P<0.001] was statistically significant (F=158.993, P<0.001). The area under the working characteristic curve of BALF miR-125a-5p level for the diagnosis of silicosis was 0.947 (95%CI: 0.887~0.981), and the sensitivity and specificity of BALF miR-125a-5p level for the diagnosis of silicosis were 89.29% and 90.57%, respectively. In the silicosis group, 31 cases (55.36%) were stage Ⅰ, 16 cases (28.57%) were stage Ⅱ, and 9 cases (16.07%) were stage Ⅲ. The levels of BALF miR-125a-5p in patients with stage Ⅰ2.36(1.84, 3.26), stage Ⅱ3.50 (3.26, 4.10), and stage Ⅲ4.25 (3.50, 4.42) silicosis were significantly higher than those in the control group 1.06 (0.62, 1.32) (H=70.774, P<0.001), and the levels of BALF miR-125a-5p in stage Ⅰ to Ⅲ silicosis patients increased stage by stage. The median value of BALF miR-125a-5p in patients with silicosis was 3.26. In patients with BALF miR-125a-5p≥3.26, VC[(69.71±5.33)% vs. (75.50±2.44)%, t=5.161, P<0.001], FEV1[ (78.24±12.20)% vs. (85.39±13.10)%, t=2.115, P=0.039], FVC[(71.39±11.25)% vs. (80.64±12.39)%, t=2.928, P=0.005] and DLCO[ (61.22±11.12)% vs. (72.19±14.82)%, t=3.147, P=0.003] were lower than those in patients with BALF miR-125a-5p<3.26. Patients with BALF miR-125a-5p≥3.26 had a high probability of developing restrictive ventilator dysfunction [26(89.66%) vs. 11(40.74%), P<0.001]. Spearman rank correlation analysis showed that the expression level of BALF miR-125a-5p was positively correlated with the levels of interleukin (IL) -5, IL-6, IL-17A, interferon-induced protein 10(IP-10) and tumor necrosis factor α(TNF-α) in silicosis patients (rs=0.299~0.671, P<0.05).

Conclusion

The high level of BALF miR-125a-5p is significantly correlated with the increase of silicosis severity and the decrease of lung function.

Key words: Silicosis, Bronchoalveolar lavage fluid, miR-125a-5p, Silicosis, Disease severity, Lung function
表1 两组矽肺患者临床资料比较
临床资料 对照组(n＝53) 观察组(n＝56) Z/t/χ2 P值
体质量指数[kg/m2，(±s)] 22.71±5.53 21.68±2.40 1.273 0.206
吸烟史[n(%)] 22(41.51) 38(67.86) 7.639 0.006
饮酒史[n(%)] 26(49.06) 30(53.57) 0.222 0.637
暴露年限[年，(±s)] 17.85±5.29 18.62±6.71 0.663 0.509
BALF参数        
总细胞计数[×107/ml，(±s)] 10.46±3.39 10.24±3.27 0.345 0.731
中性粒细胞百分比[%，(±s)] 50.66±14.81 59.16±17.82 2.700 0.008
淋巴细胞百分比[%，(±s)] 36.17±12.84 42.88±12.65 2.748 0.007
影像学结果[n(%)]        
磨玻璃影 5(9.43) 19(33.93) 9.515 0.002
实变影 2(3.77) 16(28.57) 12.151 0.000
点片状影 9(16.98) 20(35.71) 4.894 0.027
纤维索条影 4(7.55) 24(42.86) 17.782 0.000
胸膜增厚 4(7.55) 15(26.79) 7.002 0.008
肺功能指标[%，(±s)]        
VC 87.71±11.17 72.34±5.13 9.313 0.000
FEV1 95.18±10.80 81.69±13.03 5.867 0.000
FVC 89.80±9.40 75.78±12.63 6.545 0.000
FEV1/FVC 83.59±7.49 79.64±8.10 2.639 0.010
DLCO 74.03±17.32 65.72±13.72 2.784 0.006
RV/TLC[M50(P25，P75)] 22.00(17.00，27.25) 23.00(18.50，28.00) －0.439 0.661
BALF miR-125a-5p[M50(P25，P75)] 1.06(0.62，1.32) 3.26(2.25，3.82) －8.052 0.000
表2 BALF miR-125a-5p诊断矽肺Logistics回归分析
影响因素 β SE Walds值 HR(95%CI) P值
吸烟史(0＝否，1＝是) 1.480 0.493 9.003 4.395(1.671~11.559) 0.003
中性粒细胞百分比 0.064 0.053 1.498 1.067(0.962~1.182) 0.221
淋巴细胞百分比 0.077 0.132 0.336 1.080(0.833~1.399) 0.562
VC 0.042 0.053 0.641 1.043(0.941~1.156) 0.423
FEV1 －0.601 0.329 3.329 0.548(0.287~1.046) 0.068
FVC 0.466 0.292 2.538 1.593(0.898~2.826) 0.111
FEV1/FVC 0.691 0.354 3.822 1.996(0.998~3.991) 0.051
DLCO 0.001 0.032 0.000 1.001(0.939~1.066) 0.986
BALF miR-125a-5p 3.868 1.218 10.085 47.848(4.396~520.783) 0.001
图1 矽肺患者BALF miR-125a-5p与细胞因子关系矩阵散点图注：IL为白细胞介素-6；TNF-α为肿瘤坏死因子α；IP-10为干扰素诱导蛋白10
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