| Silicosis is a systemic disease with diffuse pulmonary fibrosis, and it is a result of long-term occupational exposure to vocational activities dust retention in the lungs. The main pathological changes of silicatosis in lung are fibroblast proliferation and collagen deposition. From present discovery, all kinds of cytokines play important role in the fibrosis forming. These cytokines include two kinds of the promoting fibrosis cytokines and the suppressing fibrosis cytokines. They cooperate and compete mutually to make the tissue damage or restore. The Silicosis is a disease of the lung's function damaged, because of the unbalance of these cytokines's action. In these cytokines, TGF-β1 is the strongest promotion factors of the extracellular matrix deposition and recognized as the crucial cytokine now. As the important regulation factors of TGF-βin intra-cellullar signal transduction, Smads could transduct TGF-βsignal from plasma membrane to nucleus. Smad7 which characterized as the major negative regulator is the rejecter of TGF-βmessage. Smad7 inhibit receptor mediated Smad2/3 phosphorylation by action with TGF-βreceptor directly, then hamper TGF-βsignal transduction.N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a physiological hemoregulatory inhibitor, which constituted with four amino acid residues. Recently, the function of AcSDKP on inhibiting fibrosis has been confirmed. AcSDKP can inhibit deposition of collagen and proliferation of fibroblasts of heart and kidney. In recent study, we have proved that AcSDKP could suppress macrophage aggregation and proliferation of fibroblasts and the expression and synthesis of collagen in silicotic rats. The purpose of this study is to observe AcSDKP's influence on expression of TGF-β1 and Smad7 and hematological system in silicotic rats in order to provide some basis for exploring a new way of inhibiting silicosis pulmonary fibrosis.Objectives:1. To study the relation between the expressions of TGF-β1 and Smad7 and forming and development of silicotic fibrosis.2. To investigate the regulation of AcSDKP on the expressions of TGF-β1and Smad7 in Lung of Rats with Silicosis.3. To illuminate the mechanism of AcSDKP on inhibiting silicosis and provide some theory and experimental base.Methods:1. Rats were instilled with silica through trachea as silicotic models in the experiment.2. The expression of TGF-β1 and Smad7 in lung was measured by immunohistochemistry and western blot.3. Influence of AcSDKP on hematological system was observed by measurement of blood cells and bone marrow. Meanwhile, the plasma concentration of AcSDKP was detected.4. Groups of experimental animals:①control 1 of silicotic model/control 1: each rat was instilled with 1.0ml normal sodium through trachea and was killed after 4 weeks.②control 2 of silicotic model/control 2: each rat was instilled with 1.0ml normal sodium through trachea and was killed after 8 weeks.③silicotic model 1/model 1: each rat was instilled with 50mg silica through trachea and was killed after 4 weeks.④silicotic model 2/model 2: each rat was instilled with 50mg silica through trachea and was killed after 8 weeks.⑤anti-fibrosis treating/treating 1: after each rat was instilled with 50mg silica for 4 weeks through trachea, AcSDKP(800ug·kg-1·d-1) was administered into every rat and rats were killed at the eighth week.⑥preventative treating/treating 2: after AcSDKP(800ug·kg-1·d-1) was administered into every rat for 48 hours, each rat was instilled with 50mg silica through trachea and rats were killed at the eighth week.5. Results were analyzed statistically by One-way ANOVA. To carry out the correlation analysis with immunohistochemistry results of TGF-β1 and Smad7.Results:1. Compared with the control group, the expression of TGF-β1 increased but Smad7 decreased in Lung of Rats with Silicosis.2. Compared with the silicotic model, AcSDKP(include anti-fibrosis treating and preventative treating)could raise TGF-β1 expression but reduce Smad7 expression.3. Compared with control group, the chosen dose of AcSDKP doesn't have any disadvantages on hematological system.Conclusion:AcSDKP could increase the expression of TGF-β1 but decrease the expression of Smad7. AcSDKP play possibly an important role in anti- silicotic fibrosis by increasing the expression of Smad7 to inhibit activation of TGF-βsignal transduction. |
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