The Mechanism Of Pulmonary Fibrosis Induced By Uranium Ore Dust In Rats

Objective: To explore the effect and the relevant mechanism of pulmonary fibrosis induced by uranium ore dusts in rats.Methods: 60 adult Wistar rats, male and female in half, were divided into two groups according to the principles of randomized, control group and uranium ore dust group. Non-exposed endotracheal instillation method was used. Uranium ore dust group was exposed 20mg/ml uranium ore dust suspension each rat of 1ml, meanwhile control group was exposed normal saline each rat of 1ml. Post-exposed the 7 d,14 d, 21d, 30 d and 60 d, 6 rats in each group were randomly killed. Meanwhile peripheral blood and lung tissue were collected. The pathological changes in lung tissue were observed by microscope, the collagenⅠandⅢin lungs were observed by polarizing microscope. The expressions of LN and TGF-β1 protein in lung tissue were observed by immunohistochemistry-SP. The levels of LN and PⅢNP in plasma were detected by Radioimmunoassay, and the level of TGF-β1 in lung homogenate and plasma were measured by enzyme-linked immunosorbent assay. The level of NO in lung homogenate and plasma were measured by nitrate reductase and the activity of NOS in lung homogenate and plasma were measured by NOS catalyzed L-Arg Determination.Results:1.The effect of pulmonary fibrosis induced by uranium ore dust was obviously. After exposed the uranium ore dust, the main manifestations in lung tissue were the inflammation in early stage.When post-30d, fibrosis in lung matrix appeared clearly, A large amount of fibrous hyperplasia was observed in the lung interstitium in the 60 day group treated by uranium ore dusts. 2. In uranium ore dust induced lung fibrosis, a large amount of the proliferatedⅠandⅢcollagen in lungs were observed. Post-exposure to uranium ore dust, the characteristics in proliferated collagen in lungs were typeⅠcollagen deposited in lung interstitium mainly in the early stage, while typeⅢcollagen increased significantly at the later period. The outline of pulmonary alveoli was disappeared, alveolus interstitium was severely broken and collagen deposition were formed in lung tissue induced by uranium ore dust. By the integrated optieal density ofⅠandⅢcollagen determined, the time of collagen increase in typeⅢwas later than typeⅠ, meanwhile the collagen content of typeⅢwas fewer than typeⅠ. We observed that the integrated optieal density of typeⅠa ndⅢcollagen in post-exposure uranium ore dust 21-60 day was significantly higher compared with the control group (P<0.05).3. In uranium ore dust induced lung fibrosis,the over expression of LN in the lung tissue (vascular, bronchi, sinuses and lungs interval basement ) were observed. The expression of LN were distributed in the lung tissue as thickening of the linear or clustere. By the integrated optieal density of LN determined, the integrated optieal density of LN at 21d, 30d and 60d post-exposure uranium ore dust was significantly higher compared with the control group (P<0.01). The increased content of LN in plasma was positively correlated with the over expression of LN in lung tissue.4. In uranium ore dust induced lung fibrosis,The expression of TGF-β1 in lung tissue in uranium group was significantly higher than control group.In the later, with the increase of pulmonary fibrosis, the positive expression of TGF-β1 in lung tissue was significantly increased. The increased content of TGF-β1 in lung homogenate and plasma was positively correlated with the over expression of TGF-β1 in lung tissue. The content of TGF-β1 in lung homogenate and plasma at 21d, 30d and 60d post-exposure uranium ore dust was significantly higher compared with the control group (P<0.05).5. In uranium ore dust induced lung fibrosis, the content of NO and the activity of NOS in lung homogenate in post-exposure uranium ore dust was increased. In uranium group, the content of NO and the activity of NOS in lung homogenate at 7d, 14d and 21d was not significantly difference compared with the control group (P﹥0.05), but that at 30d and 60d post-exposure uranium ore dust was significantly higher compared with the control group (P<0.05).Conclusions:1, Uranium ore dust can induce pulmonary fibrosis. Post-exposure to uranium ore dust, the characteristics in proliferated collagen in lungs are the type ofⅠcollagen deposited in lung interstitium mainly in the early stage, while the type ofⅢcollagen increase significantly at the later period. With the increase of pulmonary fibrosis, the content of typeⅠ,Ⅲcollagen fibers are significantly increased,the distribution are significantly spread.2, The expressions of TGF-β1 and LN have a high pecent in the process of pulmonary fibrosis, It suggest that TGF-β1 and LN have a effect in the process of pulmonary fibrosis.3, The lung homogenate NO and NOS increase in the process of fibrosis which consisten with the lung tissue fibrosis. And the plasma NO increase later than the lung homogenate NO.