The Effects Of Rosiglitazone And Dexamethasone On The Expression Of Caveolin-1 In The Polmonary Fibrosis Induced By Bleomycin

Objectives Observe the expression and significance of caveolin-1 in bleomycin(BLM)-induced pulmonary fibrosis and estimate the effect of rosiglitazone and dexametheasone on the expression of caveolin-1 in pulmonary fibrosis induced by bleomycin(BLM) in rats.Methods Twenty-four adult male Sprague-Dawley(SD) rats were randomly divided into four groups:the control group(C group), the bleomycin group(M group), the dexamethasone group(D group) and the rosiglitazone group(R group). Each group contained 6 rats. The model of pulmonary fibrosis was established by a single intratracheally instillation with bleomycin(5 mg/kg) except C group with the same dose of normal saline(NS) solution instead. After intratracheal instillation of BLM for 24h, rats received NS, dexamethasone or rosiglitazone by gavage per day. And each group was killed on 21th day after instillation. The lungs were harvested for hemotoxylin and eosin stain, Masson's trichrome stain and determination of hydroxyproline content. Then we observed the distribution and the expression of caveolin-1 through immunohistochemical method in the lungs of four groups.Results 1. Applying intratracheal instillation of bleomycin, we succeeded in making the rat model of pulmonary fibrosis.2. The content of hydroxyproline (Hyp) in the lungs of rats in M group was significantly higher than that in C group (P<0.01). The contents of Hyp in D group and R group decreased obviously compared with that in M group respectively(P<0.01).3. The degree of pulmonary fibrosis in M group was severer than that in C group at the 21th day(P<0.01). The degree of pulmonary fibrosis in D group and in R group showed lighter than that in M group(P<0.01).4.The immunohistochemical studies showed that caveolin-1 was mainly observed in alveolar epithelial cell, lung fibroblast, and vascular endothelial cell in lung tissues with a high level expression in C group. The expression of caveolin-1 of the lung tissues in M group was decreased significantly compared with that in C group at the 21th day (p<0.01).The expressions of caveolin-1 of lung tissues in D group and R group were higher than that in M group (P<0.01),but still lower than that in C group (P<0.01). Conclusions 1. The mechanism of downreglation of the expression of caveolin-1 may participate in pulmonary fibrosis induced by bleomycin.2. Both rosiglitazone and the low-dose dexamethasone can upregulate the expression of caveolin-1,then diminish the extent of pulmonary fibrosis induced by bleomycin and decrease the accumulation of extracellular matrix proteins. It suggests that caveolin-1 can become the new target in the treatment of pulmonary fibrosis.