| Background:Generally speaking, pulmonary fibrosis / interstitial lung disease is the final termination in which the development of many chronic lung diseases result. Because of its high mortality, the disease has been a serious threat to human health. At present, its etiology and pathogenesis is still unclear so that there is no effective treatment. Despite that it is irreversible to pulmonary fibrosis; interstitial lung disease itself is a chronic, progressive pathological process. It is widely recognized that transforming growth factor-β(TGF-β), a multifunctional cytokine, plays an important part in progressive multiple organs and tissue fibrosis. It is important that TGF-βsignalling for the initation and development of pulmonary fibrosis in human and model animals. Now, it is focused on that the role of TGF-βin pulmonary fibrosis process. It is significant to block and delay the development of pulmonary fibrosis that investigating mechanism of the pathogenesis and new interventional targets. As the development of research, the study of TGF-βreceptor (TβR), has become the focus.TβR-I, activin receptor-like kinases , include ALK-1,ALK-2,ALK-3,ALK-4,ALK-5,ALK-6 and ALK-7 in mammalian. TGF-βsignals actives Smad pathway by activating serine / threonine kinases to exert its physiolo- gical function. It is indicated that Smad2 and Smad3 play important role in TGF-β-induced fibrosis. TGF-βis activated and phosphorylating Smad2 and Smad3 by combining with ALK-5. Panopoulou E et al reported that TGF-βsignalling pathway can be blocked by inhibiting the combination of ALK-5 and Smad3.There is few related report about the action of ALK-5 in pulmonary fibrosis process. In this process, we observed that the change of ALK-5 in normal pulmonary and pulmonary fibrosis process, using Bleomycin (BL M)-induced pulmonary fibrosis model in Sprague-Dawley (SD) rats. At the same time, the action of ALK-5 in pulmonary fibrosis was analysed. Present studies provide a basis for investigating the mechanism of pulmonary fibrosis and hunting up new intervention target.Objective:To investigate the distribution and changes of the ALK-5 in normal lung and pulmonary fibrosis process by detecting the expression of ALK-5 from 0 to 35th day in the process of BLM-induced pulmonary fibrosis, and to provide evidences for prevention and cure of the lung fibrosis.Methods: BLM-induced pulmonary fibrosis model in SD rats was introduced and the expression of ALK-5 was detected by western blotting and immunohistochemical staining (SP method). To provides a basis for investigating the mechanism of pulmonary fibrosis and hunting up new intervention target.Results: 1. The expression of ALK-5 was investigated by western blotting: In the experimental group, comparing with the normal group N, ALK-5 increased on 1-3day (OD = 1.2-3.8 times of OD value of N group, P<0.05). With the extension of time, the increase of ALK-5 become higher on 7-14day (P<0.01) after operation, ALK-5 reached to peak on 28th day (OD = 5.2 times of OD value of N group P<0.01) after operation. It decreased on 35 days after operation, but it was still higher than normal (OD = 3.2 times of OD value of N group P<0.01).2. The result of immunohistochemical implied that the expression of ALK-5 protein was little in lung tissue of SD rats. The distribution was foc- us on the alveolar epithelial cells, vascular endothelial cells and fibroblasts. In experimental group, the staining is more obvious. The expression of ALK-5 up regulated in early stage of BLM-induced pulmonary fibrosis (P <0.05). With the extension of time, the increase of ALK-5 become higher on 1-14day (MOD = 1.34-3.76 times of MOD value of N group, P<0.05) after operation, ALK-5 reached to peak on 28th day (MOD = 4.85times of MOD value of N group, P<0.01) after operation. It decreased on 35days after operation, but it was still higher than normal (MOD = 3.2 times of MOD value of N group, P<0.01).Conclusion: 1. With the extension of time, the expression of ALK-5 become higher and reached to peak on 28th day after operation in the BLM-induced pulmonary fibrosis SD rats model.2. ALK-5 participates in the process of pathogenesis and development of pulmonary fibrosis. |
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