| Background:Pulmonary fibrosis is the common result of much diffuse stroma lung disease, which has the highest fatality rate in respiratory system.At present, the cause of pulmonary fibrosis have not been clarified fully, TGF-β1is one of the main cytokines lead to pulmonary fibrosis, the main reason is matrix of the lung stroma fibroblasts secretting overly, c-Jun NH2-terminal kinases is the important signal transduction channel of TGF-β1downstream.It takes a important part in TGF-β1inducing fibroblast enhanced, transformed to myofibroblast and extracellular matrix, for example collagen I, collagen III and fibronectin.Collagen I is the important component of extracellular matrix and is stimulued by TGF-β1.The abnormal expression of JNK can affect the activity of TGF-β1and then to change the process of pulmonary fibrosis.We’ll study systematically the role of JNK in rats lung fibrosis and the effects to collagen I, further to clarity the important role of JNK signal parthway in pulmonary fibrosis.and then provide theory evidence and potential target point for the prevention and cure of clinical lung fibrosis.Objective:1.Using the bleomycin-induced pulmonary fibrosis rats, among the three groups (contrast group, model group and SP600125group), we observe the pathological changes of the lung, measure the content of hydroxyproline in lung tissue, as well as survey the levels of P-JNK、collagen I in lung tissue.2.Through the observation SP600125JNK inhibitors of rats pulmonary fibrosis of the influence of collagen I, clear JNK signal pathways in the role of pulmonary fibrosis, for clinical pulmonary fibrosis of early prevention and treatment to provide the theory basis and potential targets.Methods:Fifty-four healthy male wistar rats were randomized into three groups:contrast group (group N), pulmonary fibrosis model group (group M) and SP600125group (group I), with18rats in each group, The group M received intra-tracheal instillation of5mg/kg bleomycin (BLM) for modeling of pulmonary fibrosis, and intraperitoneal injection with DMSO0.3ml; group I received BLM in the same, and intraperitoneal injection with SP6001250.3ml (dissolved in DMSO, with15mg/Kg); group N was injected intraperitoneally with DMSO0.3ml after intratracheal instillation of saline. Every six rats in each group were sacrificed at random for pathological sections of lung on days7,14and28after modeling, respectively. The degree of pulmonary alveolitis and pulmonary fibrosis was evaluated by staining with H&E and trichrome masson staining. The level of hydroxyproline (Hyp) in the lung tissue was examined by alkaline hydrolysis, and the contents of p-JNK and Collagen I in the lung tissue was detected by using the method of immunohistochemistry.Results:1.There is no significant pathological change of the rots’ lung tissues in every time in group N. A few phlogocyte or fibroblasts can be found once in a time and the interalveolar septums are Integrity. At the7th day when the represent of alveolitis was apparent in group M, the pathological evidences demonstrated that the alveolar compartments were infiltrated by massive mononuclear cells, the interalveolar septums become widen, and become more thick, The degree of fibrosis was increased gradually, and pulmonary fibrosis was formed most obviously on the28th day when the collagen fibrous dyed blue increased in pleura, big airway or vessel wall mainly. The degree of fibrosis in group I was relived as compared with that in group M, and phlogocyte become decrease obviously.2.The content of hydroxyproline was increased gradually depending on time both in group M and group I, but that in group M was significantly higher than that in group N on the14th and28th day (P<0.01), and that in group I was significantly lower compared with group M (P<0.05).There is no significant difference on the7th day.3.The levels of p-JNK with.immunohistochemisty in lung tissue were all obviously higher in group M than those in group N (P<0.01), however those in group I were lower than in group M(P<0.05). There is no significant difference in the levels of collagen I with.immunohistochemisty in lung tissue at the7th day, but that in group M was significantly higher than those in group N on the14th and28th day(P<0.01), however those in group I were lower than in group M (P<0.05).Conclusion:INK inhibitor SP600125relieved the degree of bleomycin-induced pulmonary fibrosis and decreased the expression of collagen I protein of the lung tissue in rats by inhibiting INK signal pathway;JNK signal pathway involved in the rat of pulmonary fibrosis are reviewed and the collagen I secretion for certain regulation. |
PDF Full Text Request