目的探讨白细胞介素-1(IL-1)和肿瘤坏死因子-α(TNF-α)在稀土氧化钕(Nd2O3)粉尘所致大鼠肺损伤中的作用机制。方法无特定病原体级健康成年雄性SD大鼠195只,采用非暴露式气管内一次性灌注法建立肺损伤模型。1剂量-效应关系实验:设置25、50、100和150 mg/kg剂量组(每组15只),分别予相应剂量的Nd2O3混悬液染尘,对照组(10只)予生理氯化钠溶液处理,均于染尘后第28天处死。2时间-效应关系实验:染尘组大鼠(75只)予剂量为100 mg/kg的Nd2O3混悬液染尘,对照组大鼠(50只)予生理氯化钠溶液处理,分别于染尘后第3、7、14、21、28天各处死15和10只大鼠。称量大鼠体质量并计算肺脏脏器系数,观察大鼠肺组织病理学改变情况,酶联免疫吸附实验法测定大鼠支气管肺泡灌洗液(BALF)中IL-1和TNF-α水平。结果肺组织病理学观察显示成功建立染尘大鼠肺损伤模型。4个剂量组大鼠体质量均低于对照组(P<0.05),肺脏脏器系数和BALF中IL-1、TNF-α水平均高于对照组(P<0.05);大鼠体质量随染尘剂量的增加而减轻,肺脏脏器系数和BALF中IL-1、TNF-α水平均随染尘剂量的增加而增加,均存在剂量-效应关系(Spearman相关系数分别为-0.825、0.953、0.566和0.544,P<0.01)。大鼠体质量在染尘处理和观察时间的主效应上均有统计学意义(P<0.01),但在两者的交互效应上无统计学意义(P>0.05)。大鼠肺脏脏器系数在染尘处理与观察时间的交互效应上有统计学意义(P<0.01);其中,染尘组大鼠在5个时间点的肺脏脏器系数均高于相同时间点的对照组(P<0.05),并呈现随观察时间的增加而增加的时间-效应关系(P<0.05)。染尘组大鼠BALF中IL-1和TNF-α水平均高于对照组(P<0.01),但未发现Nd2O3粉尘染尘处理与IL-1、TNF-α水平之间存在时间-效应关系。结论稀土Nd2O3粉尘可导致大鼠发生具有剂量-效应和时间-效应关系特征的肺损伤,并可导致大鼠BALF中IL-1和TNF-α水平发生具有剂量-效应关系特征的升高,表明IL-1和TNF-α在Nd2O3粉尘所致肺损伤的发生和发展中具有一定的作用。 Objective To investigate the mechanism of interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) in lung injury induced by rare earth neodymium oxide (Nd2O3) dust in rats. Methods 195 healthy adult male Sprague-Dawley (SD) rats without specific pathogen were used to establish the model of lung injury by non-exposure endotracheal perfusion. 1 dose-effect relationship experiment: set 25,50,100 and 150 mg / kg dose group (each group of 15), respectively, the corresponding dose of Nd2O3 suspension dust, the control group (10) to physiological sodium chloride Solution treatment, were killed on the 28th day after dying. Time-effect relationship experiment: Dust-exposed rats were dusted with Nd2O3 suspension (100 mg / kg) and control group (50 rats) with physiological sodium chloride solution respectively, After the dust on the 3rd, 7th, 14th, 21st and 28th days, 15 and 10 rats were killed. The body weight of rats was weighed and the coefficients of lung organ were calculated. The pathological changes of lung tissue were observed. The levels of IL-1 and TNF-α in bronchoalveolar lavage fluid (BALF) of rats were measured by enzyme-linked immunosorbent assay. Results Lung histopathology showed that the successful establishment of lung injury model in rats with dust. The body weight of 4 dose groups were lower than that of the control group (P <0.05), the indexes of lung organ and the levels of IL-1 and TNF-α in BALF were higher than those of the control group (P <0.05) (P <0.05). The lung organ coefficient and the levels of IL-1 and TNF-α in BALF all increased with the increase of dust dose. The Spearman’s correlation coefficients were -0.825,0.953, 0.566 and 0.544, P <0.01). The body weight of rats was statistically significant (P <0.01) on the main effects of dust treatment and observation time, but there was no significant difference in the interaction between them (P> 0.05). The lung organ coefficients of rats were statistically significant (P <0.01) in the interaction between the dust treatment and the observation time. The lung organ coefficients of the rats in the dust group at 5 time points were all higher than those at the same time point (P <0.05), and showed a time-effect relationship with the increase of observation time (P <0.05). The levels of IL-1 and TNF-α in the BALF of the dust-exposed group were higher than those of the control group (P <0.01), but there was no time-effect relationship between the levels of IL-2 and TNF-α . Conclusions Rare-earth Nd2O3 dust can cause lung injury characterized by dose-effect and time-effect in rats, and lead to an increase in the dose-response characteristics of IL-1 and TNF-α in BALF of rats IL-1 and TNF-α play a role in the occurrence and development of lung injury induced by Nd2O3 dust.