| Objectives:To estimate the effort of rosiglitazone, a PPAR-y agonist, and prednisone on the dynamic expression of Fizzl in pulmonary fibrosis induced by bleomycin(BLM) in rats.Methods:ninety adult male Sprague-Dawley(SD) rats were randomly divided into five groups:the normal group (group N) bleomycin group (group B), the prednisone group (group P) rosiglitazone group(group R), prednisone and rosiglitazone group(group P+R). Each group contains 18 rats. And the animals in each group for 7th, 14th,28th days after modeling, were randomly divided into 3 subgroups, each subgroup includes 6 rats. The BPF model was established by a single dosage of 5mg/kg bleomycin intratracheal except group N with the same dose of saline (NS) solution instead. After intratracheally instillation of BLM for 24h, the rats of every groups received NS, prednisone, rosiglitazone or both prednisone and rosiglitazone by gavage per day. At 7th,14th,28th days after BLM administration, rats of per treatment group were randomly killed respectively. The lungs were harvested for hemotoxylin and eosin stain, Masson's trichorome stain and determination of hydroxyproline content. The method of immunohistochemical was used to detect the expression of fizzl.Result:1.We succeeded in reproduction of the pulmonary fibrosis through a single dosage of 5mg/kg bleomycin intratracheal injection. 2.The rats of group B showed higher lung index than that of other group (P<0.01).And the lung index of group P, group R and group P+R was lower than group B and higher than group N(P<0.01).There was no significant differences among this three treatment group in 7 days. Lung index of group P+R was lower than group P in 14 and 28days and lower than group R in 14 days; 3. HYP concentrations of group B, group P, group R and group P+R were markedly higher than group N (P<0.01),And the content of Hyp in group P,group R and group P+R decreased obviously than in group B respectively (P<0.05). There was no significant differences among group P,R and P+R. in 7 days. The content of HYP of group P+R was lower than group P in 14 days and 28days.and lower than group R in 28 days.4 The degree of alveolitis and pulmonary fibrosis of group B was higher than group N(P<0.01),P,R and P+R in each group the degree of alveolitis and fibrosis was markedly lower than group B(P<0.01). In 14days and 28days the degree of alveolitis and fibrosis in group P+R was lower than group P(P<0.05).It showed no significant difference between group P and group R as well as group R and group P+R(P>0.05).5,The result of immunohistochemistry suggested that fizzl was mainly weakly expressed in bronchial epithelium cells, aleolar epithelial typeâ…¡cells and endothelial cells in normal lung. The expression of fizz 1 protein in the lung increased after 7d in bleomycin-trected animals and was slightly decreased on 14 d and markedly decreased on 28 d than group N (P<0.05) Fizzl expression in the group of P,R,P+R had the same tendency as group B, but the concentration were lower than group B (P<0.05),and in 7days and 14days fizzl expression of group P+R was lower than group P. There was no significant difference among group P,R,P+R in 28days and between group P and group R as well as group R and group P+R.Conclusions 1.the mechanism of upregulation of the expression of fizzl may participate in pulmonary fibrosis induced by bleomycin.2 Both prednisone and Rosiglitazone can downregulate the expression of fizzl,diminish the extent of pulmonary fibrosis induced by bleomycin and decease the accumulation of extracellular matrix protein. It suggests that fizzl can become a new target in the treatment of pulmonary fibrosis. |
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