稀土氧化钕粉尘致大鼠肺纤维化过程中Ⅰ、Ⅲ型胶原及白介素-12表达的变化

Changes of typeⅠ,Ⅲ collagen and IL-12 in pulmonary fibrosis induced by rare earth neodymium oxide dust in rats

目的探讨稀土氧化钕粉尘的致纤维化过程中Ⅰ、Ⅲ型胶原纤维、白介素-12(IL-12)表达的变化特征。方法选用SPF级健康成年雄性SD大鼠70只,体重(200±16)g,采用气管非暴露插管灌注法进行染尘建立模型。实验组按25、50、100、150(mg/kg)稀土氧化钕粉尘悬液0.8 ml一次性染尘,对照组0.9%生理盐水0.8 ml。在28 d后实验组各处死大鼠15只,对照组处死10只。酶联免疫吸附试验(ELISA)法分别测定实验组大鼠支气管肺泡灌洗液(BALF)上清液中IL-12含量;肺组织采用天狼猩红染色,偏光显微镜下观察Ⅰ、Ⅲ型胶原纤维。结果稀土氧化钕粉尘致实验大鼠肺组织纤维化过程中可见Ⅰ、Ⅲ型胶原纤维的大量增生,染尘后早期主要以Ⅰ型胶原纤维增生为主。其Ⅰ、Ⅲ型胶原纤维增加与对照组比较差异均有统计学意义(P<0.05)。在实验组中大鼠BALF上清液中IL-12随着染尘剂量的增加而逐渐增多,含量均高于对照组(P<0.05)。结论稀土氧化钕粉尘在诱导大鼠肺部组织纤维化过程中,Ⅰ、Ⅲ型胶原纤维均大量增多,分布范围扩大。同时BALF上清液中IL-12出现高表达,表明IL-12在肺组织纤维化发生和发展过程中具有一定的作用。

[Objective]To explore the change characteristics of typeⅠ,Ⅲ collagen and IL-12 in pulmonary fibrosis induced by rare earth neodymium oxide dust.[Methods]70 healthy adult male SD rats（ SPF level） were applied in this study,and the body weight was（ 200 ± 16） g. The dust-exposure model was established by the method of tracheal unexposed intubation perfusion. The experimental group was treated with 0. 8 ml rare earth neodymium oxide dust suspension according to 25,50,100 and 150 mg /kg,and the control group was injected with 0. 8 ml normal saline solution 0. 9%. After 28 days,15 rats in the experimental group and10 rats in the control group were killed. The IL-12 content in supernatant of bronchoalveolar lavage fluid（ BALF） was detected by ELISA. The lung tissues were dyed by the sirius red,and the levels of typeⅠ,Ⅲ collagen were observed under polarized light microscope.[Results]The levels of typeⅠ,Ⅲ collagen significantly increased in the process of pulmonary fibrosis induced by rare earth neodymium oxide dust in rats,and typeⅠ collagen hyperplasia was predominant in the early period of dust-exposure. The levels of typeⅠ,Ⅲ collagen in the experimental group were significantly higher than those in the control group（ P〈0. 05）. The IL-12 content in supernatant of BALF in the experimental group increased with the increasing of exposure dose,and the contents were higher than that in the control group（ P〈0. 05）.[Conclusion]The levels of typeⅠ,Ⅲ collagen significantly increase in the process of pulmonary fibrosis induced by rare earth neodymium oxide dust in rats,with distribution and range expansion. Meanwhile,the high expression of IL-12 has been observed in supernatant of BALF,which indicated that IL-12 plays a certain role in the process of the occurrence and development of the lung tissue fibrosis.