Objective: To observe the changes of lung function and inflammatory factors in rat models of coal workers\' pneumoconiosis at different time points. Methods: In June 2021, 96 healthy male SD rats with SPF grade were divided into 1, 3, and 6-month control group and dust staining group (coal dust group, coal silica dust group, quartz group) according to random number table method, with 8 rats in each group. After one week of adaptive feeding, a one-time non-exposed tracheal perfusion method (1 ml/ piece) was used. The dust dyeing group was given 50 g/L coal dust, coal silica mixed dust and quartz dust suspension, respectively, and the control group was given 0.9% normal saline solution. At 1, 3 and 6 months after perfusion, lung function was detected by animal lung function apparatus, then all lung tissues and alveolar lavage fluid were killed, and lung histopathological morphological changes were observed by HE staining, and the contents of interleukin (IL-1β), IL-18, IL-4 and IL-10 in alveolar lavage fluid were detected by ELISA. One-way analysis of variance was used to compare groups. Two factors (inter-group treatment factor (4 levels) and observation time factor (3 levels) ) were used in the analysis of the effects of inter-group treatment and treatment time on related indicators. Results: HE staining results showed that coal spot appeared in the lung tissue of coal dust group, coal spot and coal silicon nodule appeared in the lung tissue of coal dust group, and silicon nodule appeared in the lung tissue of quartz group. Compared with the control group, the forced vital capacity (FVC) and forced expiratory volume at 0.2 second (FEV(0.2)) of rats in the dust staining group had interaction between the treatment and treatment time (P<0.05). With the increase of dust dyeing time, FVC and FEV(0.2) decreased significantly at 3-6 months of dust dyeing, and the maximum gas volume per minute (MVV) decreased significantly at 1-3 months of dust dyeing (P<0.05). The lowest lung function index was in quartz group, followed by coal-silica group and coal-dust group. There were statistically significant differences in the main effect and interaction effect of the pro-inflammatory factor IL-18 among all groups in treatment and treatment time (IL-18: F=70.79, 45.97, 5.90, P<0.001), and interaction existed. The highest content of inflammatory factors in alveolar lavage fluid of all dust groups was quartz group, followed by coal silica group and coal dust group. There were significant differences in the main effect and interaction effect of anti-inflammatory factors between groups and treatment time (IL-4: F=41.55, 33.01, 5.23, P<0.001, <0.001, <0.001; IL-10: F=7.46, 20.80, 2.91, P=0.002, <0.001, 0.024), and there was interaction. The highest content of anti-inflammatory factor was in quartz group, followed by coal silica group and coal dust group. Conclusion: Lung function decreased and levels of inflammatory fators increased in rat models of coal workers\' pneumoconiosis, with the quartz group being the most severely damaged. Lung function is mainly impaired in thrid-six months, and the content of inflammatory factors begins to change in first-thrid months. MVV are the earliest and most obvious in lung function. IL-18 is suitable for monitoring changes in the pro-inflammatory response of coal workers\' pneumoconiosis, and IL-10 is suitable for monitoring changes in anti-inflammatory response.
目的: 观察不同时间点大鼠煤工尘肺模型肺功能与炎症因子的变化特点。 方法: 于2021年6月,将96只SPF级健康雄性SD大鼠按随机数字表法分为1、3、6个月对照组和染尘组(煤尘组、煤矽尘组、石英组),每组8只。适应性饲养一周后,采用一次性非暴露式气管灌注法(1 ml/只),染尘组分别给予50 g/L煤尘、煤矽混合尘和石英尘悬浮液,对照组给予0.9%生理盐水溶液。灌注后满1、3、6个月时采用动物肺功能仪检测肺功能,随后全部处死大鼠并取肺组织和肺泡灌洗液,HE染色观察肺组织病理学形态变化,ELISA法检测肺泡灌洗液中细胞介素(IL)-1β、IL-18、IL-4和IL-10的含量。多组间比较用单因素方差分析;组间处理和处理时间对相关指标的影响分析采用两因素[组间处理因素(4个水平)、观察时间因素(3个水平)]4×3析因设计方差分析。 结果: HE染色结果显示,煤尘组大鼠肺组织出现煤斑,煤矽尘组大鼠肺组织出现煤斑和煤矽结节,石英组大鼠肺组织出现矽结节。与对照组比较,各染尘组大鼠用力肺活量(FVC)、第0.2秒用力呼气容积(FEV(0.2))在组间处理和处理时间上存在交互作用(P<0.05)。随着染尘时间的增加,FVC、FEV(0.2)在染尘3至6个月时明显下降,每分钟最大通气量(MVV)在染尘1至3个月时明显下降(P<0.05)。各染尘组大鼠肺功能指标最低的是石英组,其次为煤矽尘组、煤尘组。各组大鼠促炎因子IL-18在组间处理和处理时间的主效应及交互效应上差异均有统计学意义(F=70.79、45.97、5.90,P均<0.001),且存在交互作用。各染尘组肺泡灌洗液中炎症因子含量最高的是石英组,其次为煤矽尘组、煤尘组。各组大鼠抗炎因子在组间处理和处理时间的主效应及交互效应上差异均有统计学意义(IL-4:F=41.55、33.01、5.23,P=<0.001、<0.001、<0.001;IL-10:F=7.46、20.80、2.91,P=0.002、<0.001、0.024),且存在交互作用。各染尘组大鼠抗炎因子含量最高为石英组,其次为煤矽尘组、煤尘组。 结论: 大鼠煤工尘肺各类型均出现肺功能下降和炎症因子含量升高,其中石英组损害最为严重。肺功能主要在3至6月出现损害,炎症因子含量在1至3月就开始发生变化。肺功能指标MVV变化最早、最明显,IL-18适合监测煤工尘肺促炎反应变化,IL-10适合监测抗炎反应变化。.