The Study Of Fluvastatin In Bleomycin-induced Pulmonary Fibrosis Of Rats

Objective: To investigate the effects of fluvastatin on the proliferation of the fibroblasts from rat lung in vitro and in bleomycin-induced pulmonary fibrosis of rats in vivo. Methods: In vitro, normal rat lung-derived fibroblasts were cultured in media containing fluvastatin. The influences on the growth curve and the division index of the fibroblasts were observed by cell counting and MTT; the inhibition of serial dilutions of fluvastatin on the fibroblasts was investigated by MTT; with serial dilutions of fluvastatin, we also detected the hydroxyproline in the media; In vivo, thirty SD rats were divided into six groups: the normal control group (Group C), the model group treated with bleomycinA5 (Group B) and the rest (Groups TH1, TL1, TH15 and TL15) so named according to the date which were the first and the fifteenth day after the rats were given bleomycinA5 and the dose of fluvastatin which were 20 mg ?kg"1 and 10 mg ?kg"1 respectively. All the rats were killed on the twenty-eighth day. The number of fibroblast and the thickness of alveolar wall, the area of mesenchyma in lung tissue were measured by HE staining. The extracellular matrix and I ,111 typecollagen in lung tissue were observed by Masson and sirius red staining and hydroxyproline was measured in lung tissue homogenates.Results: Fluvastatin could inhibit the proliferation of the fibroblasts from normal rat lung (PO.01). With the concentration of 10~4M of fluvastatin, the A490nm of the fibroblasts by MTT was not different to the fibroblasts without fluvastatin (P>0.05) and with serial dilutions of fluvastatin, we found a concentration-dependent increase in the proliferation of the fibroblasts and a concentration-dependent increase of the hydroxyproline in the media. The division index of the fibroblasts was also found decreased with fluvastatin of 10"5M and 10"4M(P<0.01). In vivo, the number of fibroblast and the thickness of lung alveolar wall, the area of mesenchyma and the content of hydroxyproline in lung tissue were significantly higher in Group B than those in Group C (P<0.01). The data in the treatment groups were lower than those in Group B (PO.01 or PO.05). It was also found that the data of HE staining were lower in Group TH1 than in Group TH15 (PO.01) and in Group TL1 than in Group TL15 (PO.Olor PO.05). In addition, the extracellular matrix and I ,111 type collagen in lung tissue were more in group B than those in group C, and compared with group B, they were less in the treatment groups. Conclusions: Fluvastatin could inhibit the proliferation of the fibroblasts from the normal rat lung in vitro and has therapeuticeffect to bleomycin-induced pulmonary flbrosis of rats in vivo. It might be a effective drug for pulmonary flbrosis.