铀矿尘对大鼠肺组织及血浆中转化生长因子-β1和一氧化氮水平影响

Changes and correlation of transforming growth factor-β1 and nitric oxide in lung tissue and plasma in pulmonary fibrosis induced by uranium ore dust in rats

目的探讨铀矿尘致大鼠肺纤维化过程中,肺组织和血浆中转化生长因子-β1(TGF-β1)、一氧化氮(NO)水平变化。方法 60只成年Wistar大鼠,随机分为铀矿尘组与对照组。采用一次性非暴露式气管灌注法,铀矿尘组一次性气管内灌注质量浓度为20 g/L铀矿粉尘悬液1 ml,对照组一次性气管内灌注生理氯化钠溶液1 ml。每组分别于染尘后第7、14、21、30及60天随机处死6只动物,取周围血及肺组织。肺组织形态学观察采用HE染色法;肺组织及血浆中TGF-β1水平的测定采用酶联免疫吸附法(ELISA法);肺组织及血浆中NO水平的测定采用硝酸还原酶法。结果实验观察期内铀矿尘致大鼠肺组织纤维增生病变;铀矿尘在致肺组织纤维化过程中,可引起肺组织及血浆中TGF-β1及NO水平增高,且在染尘后第30、60天时其肺组织和血浆中TGF-β1及NO水平与对照组比较,差异有统计学意义(P<0.05);肺组织与血浆中TGF-β1及NO水平变化存在直线正相关(rTGF=0.887,P<0.05;rNO=0.958,P<0.05)。结论在铀矿尘致大鼠肺纤维化过程中,其肺组织和血浆中TGF-β1和NO的水平可见明显增高,肺组织与血浆中TGF-β1及NO水平变化存在直线正相关。

Objective To study the changes of transforming growth factor-β1 （ TGF-β1 ） and nitric oxide （NO） contents in lung tissue and plasma in pulmonary fibrosis induced by uranium ore dust in rats. Methods 60 adult Wistar rats were randomly divided into a control group and a uranium ore dust group. Each rat in uranium ore dust group was exposed to 1 ml （20 g/L） of uranium ore dust suspension for once, while each rat in the control group was exposed to 1 ml of normal saline. 7, 14, 21,30 and 60 days after the exposure, 6 rats in each group were randomly killed and lung tissues and plasma were collected. The levels of TGF-β1 in lung homogenates and plasma were determined by ELISA; the contents of NO in lung homogenates and plasma were determined by nitric acid reductase method to make a correlation analysis of the results. Results In uranium ore dust group, lung tissue inflammation in early stage and lung fibrosis in late stage were obviously observed. In the process of pulmonary fibro- sis induced by uranium ore dust, the contents of TGF-I^I and NO in lung tissues and plasma were increased. The levels of TGF- β1 and NO in lung tissues and plasma in the rats 30 and 60 days after the exposure were significantly higher （ P 〈 0.05 ） than those of the control group. The correlation analysis showed that the changes of TGF-β1 and NO content in lung tissue and plasma had a positive correlation （ rTGF = 0. 887, P 〈 0.05 ; rNo = 0. 958, P 〈 0.05 ）. Conclusion The contents of TGF-β1 and NO in lung tissue and plasma are increased obviously in the process of lung fibrosis induced by uranium ore dust. There is a positive as- sociation between the levels of TGF-β1 and NO in lung tissue and plasma.