Objective: To study the effect of samarium trioxide (Sm(2)O(3)) particles on rat lung tissue and compare it with the same dose of silica (SiO(2)) particles, in order to find the reference index for early screening of pneumoconiosis. Methods: In October 2018, 72 SPF healthy male rats were randomly divided into control group, SiO(2) group and Sm(2)O(3) group. The lungs of rats in each group were perfused with 2.0 ml/kg normal saline and 280 mg/kg SiO(2) and Sm(2)O(3) particle suspension by one-time non exposed tracheal perfusion. The lungs of rats were stained with hematoxylin eosin (HE) staining, and the pathological changes of lung tissues were observed. The concentrations of SNAIL homologue 1 (SNAI1) , SNAIL homologue 2 (SNAI2) , and heat shock protein-27 (HSP-27) in rat serum were detected by enzyme-linked immunosorbent assay. 0.5 g of lung tissue from rats in Sm(2)O(3) group and control group exposed to dust for 56 days was screened for long-chain noncoding RNA (lncRNA) and circular RNA (circRNA) . Results: After 7 days of dust exposure, the alveoli in SiO(2) group and Sm(2)O(3) group were disordered, and lymphoid tissue aggregation and proliferation were observed around the bronchial wall. At 14 days, a large number of lymphocytes infiltrated in SiO(2) group, and a small number of macrophages containing Sm(2)O(3) and fibrotic nodules scattered in Sm(2)O(3) group. At 28 days, a small amount of lymphocyte infiltration appeared in SiO(2) group, and fibrotic nodules were seen in some areas of Sm(2)O(3) group. At 56 days, there was a small amount of fibroblast proliferation in SiO(2) group, and a large number of fibrotic nodules containing gray black matter were seen in Sm(2)O(3) group. There was no significant difference in lung organ coefficient among groups at different dust exposure time (P>0.05) . After 14 days of dust exposure, the contents of SNAI1 and SNAI2 in serum of rats in SiO(2) group were lower than those in control group, the content of SNAI2 in serum of Sm(2)O(3) group was lower than that in control group, and the contents of SNAI1 and SNAI2 in serum of Sm(2)O(3) group were higher than those in SiO(2) group (P<0.05) . The content of HSP-27 in SiO(2) group was lower than that in control group (P<0.05) . After 56 days of dust exposure, the content of HSP-27 in Sm(2)O(3) group was lower than that in control group (P<0.05) . At 56 days, lncRNA in Sm(2)O(3) group was up-regulated by 148 and down regulated by 725, circRNA was up-regulated by 16 and down regulated by 153. Conclusion: Sm(2)O(3) can cause lung injury in rats, and the change of SNAI2 content can be detected in the early stage, which can be used as a reference index for early screening of pneumoconiosis. There are differences in the expression of lncRNA and circRNA after 56 days of dust exposure in rats, which may be related to the pathogenesis of pneumoconiosis.
目的: 研究三氧化二钐(Sm(2)O(3))微粒对大鼠肺组织的影响,并与相同剂量的二氧化硅(SiO(2))微粒比较,以期寻找尘肺病的早期筛检参考指标。 方法: 于2018年10月,将72只SPF级健康雄性大鼠以完全随机分组法分为对照组、SiO(2)组、Sm(2)O(3)组,采用一次性非暴露式气管灌注法分别向各组大鼠肺部灌注2.0 ml/kg生理盐水和280 mg/kg的SiO(2)、Sm(2)O(3)微粒悬浮液。用苏木精-伊红(HE)染色法染色大鼠肺脏,观察大鼠肺组织病理改变。采用酶联免疫吸附法检测大鼠血清中SNAIL同源物1(SNAI1)、SNAIL同源物2(SNAI2)、热休克蛋白-27(HSP-27)浓度。取染尘56 d Sm(2)O(3)组、对照组大鼠肺组织0.5 g进行长链非编码RNA(lncRNA)、环状RNA(circRNA)筛检。 结果: 染尘7 d时,SiO(2)组和Sm(2)O(3)组大鼠肺泡排列紊乱,围绕支气管壁可见淋巴组织聚集增生;14 d时SiO(2)组有大量淋巴细胞浸润,Sm(2)O(3)组分散存在少量含Sm(2)O(3)的巨噬细胞及纤维化结节;28 d时SiO(2)组出现少量淋巴细胞浸润,Sm(2)O(3)组部分区域可见纤维化结节;56 d时SiO(2)组有少量纤维母细胞增生,Sm(2)O(3)组可见大量含灰黑色物质的纤维化结节。不同染尘时间各组大鼠肺脏系数差异均无统计学意义(P>0.05)。染尘14 d时SiO(2)组大鼠血清中SNAI1、SNAI2含量低于对照组,Sm(2)O(3)组血清中SNAI2含量低于对照组,但SNAI1、SNAI2含量高于SiO(2)组(P<0.05);染尘28 d时SiO(2)组HSP-27含量低于对照组(P<0.05)。染尘56 d后,Sm(2)O(3)组HSP-27含量低于对照组(P<0.05)。染尘56 d后,Sm(2)O(3)组lncRNA上调148个、下调725个,circRNA上调16个、下调153个。 结论: Sm(2)O(3)可致大鼠肺损伤,早期即可检测到SNAI2含量的改变,可以作为尘肺病的早期筛检参考指标。大鼠染尘56 d后lncRNA、circRNA表达有差异,可能与尘肺病的发病机制有关。.
Keywords: Circular RNA; Heat-shock proteins; Long non-coding RNA; Lung injury; Rats; Recombinant snail homolog 1; Recombinant snail homolog 2; Samarium trioxide; Silicon dioxide.