| Pulmonary fibrosis, the pathogenesis of which is mainly the imbalance of extracelluar matrix metaboism and its over-deposition in the lung, is the final common sequel to a variety of diffuse interstitial lung diseases. Current treatment, comprising corticosteroids with or without immunosuppressants, has not improved the poor prognosis and mortality from the disease is increasing steadily, so there is a compelling need to develop new therapeutic agents. Considerable evidences have suggested that TGF-β1/Smad4 signal transducting pathway has played a key role in the pathogenesis of pulmonary fibrosis and interests have focused on the thrapy of fibrosis disease through blocking this pathway. Sodium ferulate is the sodium salt of ferulic acid which is the main component of ligustrazine and angelica root. Datas have emerged suggesting that sodium ferulate can resist the effects of ET-1, inhibit the recruitment of platelet and increase the ability of antioxidant, et al. The purpose of this study was to investigate the effect and mechanism of sodium ferulate on pulmonary fibrosis in bleomycin-induced rats by observing changes of collagen metabolism and TGF-β1/Smad4 signal transducting pathway and provide the theoretic evidence for developing the effecive therapeutic agents to pulmonary fibrosis in traditional Chinese medicine. Part 1Modulating effect of sodium ferulate on imbalance of collagen metabolism in the lung tissue of rats with pulmonary fibrosisObjective: To explore modulating effect of sodium ferulate on imbalance of collagen metabolism in rats with pulmonary fibrosis. Methods: Thirty SD rats were randomly divided into control group, pulmonary fibrosis group and sodium ferulate group. A rat model of pulmonary fibrosis was established by the intratracheal injection of bleomycin(5mg/kg). Sodium ferulate was administered intragastricly in sodium ferulate group with a dose of 150mg/kg. The lung histopathology and cell counting were examined by HE staining; Collagen fibril staining was used to detect the expression of the total collagen quantity and immunohistochemical assay was used to detect typeⅠcollagen quantity. Results: Compared with the control group,cell counting and the expression of the total collagen quantity and typeⅠcollagen quantity in the pulmonary fibrosis group were significantly higher (22243.60±5011.55 vs 11496.89±5598.97, P＜0.001; 0.96±0.37 vs 0.23±0.15, P＜0.001; 0.97±0.34 vs 0.27±0.08, P＜0.001, respectively). While compared with the pulmonary fibrosis group, cell counting and the expression of the total collagen quantity and typeⅠcollagen quantity in the sodium ferulate group were significantly lower (14992.04±5593.80 vs 22243.60±5011.55, P＜0.01; 0.33±0.21 vs 0.96±0.37, P＜0.001; 0.39±0.25 vs 0.97±0.34, P＜0.001, respectively). Conclusions: Sodium ferulate can effectively reduce the degree of inflammation and deposition of collagen in the lung tissue of rats with plumonary fibrosis, so it has an inhibitory effect on pulmonary fibrosis. Part 2Effect of sodium ferulate on expression of TGF-β1 signal transduction molecule mRNA in the lung tissue of rats with pulmonary fibrosisObjective: To investigate the effect of sodium ferulate on the expression of TGF-β1 singal transduction molecule mRNA in the lung tissue of rats model of pulmonary fibrosis and explore the mechanism of sodium ferulate on pulmonary fibrosis. Methods: Thirty SD rats were randomly divided into control group, pulmonary fibrosis model group and sodium ferulate group. The lung histopathology was examined by HE staining; In situ hybridization was used to detect the expression of TGFβRⅡand Smad4 mRNA in the lung tissue and real-time fluorescence-quantification RT-PCR was used to detect the expression of TGF-β1 mRNA in the lung tissue. Results: HE staning indicated that the structure of the control group lung tissue were normal and there were no inflammtory cells in the pulmonary alveolus. There were lots of inflammatory cells in the pulmonary alveolus of model group and fiber tissue increase seriously. There were less inflammatory cells in the lung tissue of sodium ferulate group than that of model group, the pulmonary alveolus structure was not changed much in sodium ferulate group. The expression of pulmonary TGF-β1 mRNA, TGFβRⅡmRNA and Smad4 mRNA in model group were significantly higher than that in control group (0.0170±0.0157 vs 0.0025±0.0030, 0.18±0.08 vs 0.07±0.04, 0.17±0.10 vs 0.07±0.03, respectively, all P＜0.01), while the expression of pulmonary TGF-β1 mRNA,TGFβRⅡmRNA and Smad4 mRNA in sodium ferulate group were significantly lower than that in model group (0.0058±0.0094 vs 0.0170±0.0157, 0.13±0.04 vs 0.18±0.08, 0.11±0.03 vs 0.17±0.10, respectively, all P＜0.05)Conclusions: Sodium ferulate can effectively inhibit the expression of the TGF-β1 mRNA,TGFβRⅡmRNA and Smad4 mRNA in the lung tissue, thus it has a resistive effect on pulmonary fibrosis.Conclusions:1. Sodium ferulate has a resistive effect on pulmonary fibrosis in rats induced by bleomycin;2. The resistive effect of sodium ferulate is related with its inhibiting the expression of TGF-β1 mRNA,TGFβRⅡmRNA and Smad4 mRNA in lung tissues of rats with pulmonary fibrosis.
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