PPARγ Agonist And Dexamethasone Alleviate The Pulmonary Fibrosis Induced By Bleomycin Through Upregulating Pulmonary Glucocorticoid Receptors In Rats

Objectives To examine the effect of rosiglitazone, PPARy agonist, on pulmonary fibrosis induced by bleomycin (BLM) in rats.Methods Thirty adult male Sprague-Dawley rats were divided randomly into five groups:the control group(group C), the bleomycin group(group M), the rosiglitazone group(group R), the dexamethasone group(group D), the rosiglitazone and dexamethasone group(group R+D). Group C was intratracheally instilled with normal saline(NS), while the other groups instilled with BLM solution.After the intratracheal instillation of BLM for 24h, rats received NS, dexamethasone, rosiglitazone or uniting dexamethasone and rosiglitazone by gavage per day. All rats were killed on the 21th day. The lungs were harvested for hemotoxylin and eosin stain, Masson's trichrome stain and determination of hydroxyproline content. The method of immunehistochemistry was used to detect the expressive levels of glucocorticoid receptor (GR).Results (1)We succeeded in reproduction of the pulmonary fibrosis through intratracheal instillation of bleomycin. (2)There was no significant difference in weight between group Dand group R+D(P>0.05). The weight of group R was lower than that of group C (P<0.01), but higher than that of group Dand group R+D (P<0.01). (3)The contents of hydroxyproline in group R and group D were significantly lower than that in group M (P<0.01), but higher than that in group D+R (P<0.05). (4) The dgree of pulmonary fibrosis in lung tissue was observed by Masson's trichrome stain:The degree of pulmonary fibrosis in group M are the more severer than that in group P at the 21th day(P<0.01). The degree of pulmonary fibrosis in group R and group D were significantly lower than that in group M (P<0.01), but higher than that in group D+R (P<0.05). (5)The immunohistochemical studies showed that the glucocorticoid receptor can be seen in airways, alveolar epithelial cell, fibroblast, inflammatory cells and blood vessels in lung tissues, with positive staining mainly at the nuclei and some in the plasma. The result of average integrated optical density analysis showed that the expression level of GR in group M was significantly lower than that in group C (P<0.01). The expression of GR in lung tissue of group R and group D was markedly higher than that of M group (P<0.01), but lower than that of group D+R(P<0.01).Conclusions Rosiglitazone, PPARy agonist, could upregulate the expression of GR in the lung, and alleviate the bleomycin induced pulmonary fibrosis in rats. Utilizing rosiglitazone and dexamethasone could enhance the effects on treating the lung fibrosis. Rosiglitazone didn't inhibit the increase of the weight of rats. It suggests that rosiglitazone could be a therapeutic way for pulmonary fibrosis.