Effects Of Different Doses Of Atorvastatin On Pulmonary Fibrosis Of Rats

Backgroud and ObjectivesPulmonary fibrosis is a disease whose origin and pathogenesy are unknown. Recently, it was reported that both incidence rate and case-fatality rate of pulmonary fibrosis upgrade obviously. But there are still no available therapeutic methods now. Therefore my research in which the method of instilling bleomycin in trachea one time is used to mimic the modle of pulmonary fibrosis of rats is to observe the effects of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) on pulmonary fibrosis and the therapeutic effects of different doses of atorvastatin on bleomycin (BLM)-induced pulmonary fibrosis of rats.Materials and MethodsSeventy-five healthy female SD rats were randomly divided into five groups (15 rats in each group) ie. normal group; bleomycin-induced pulmonary fibrosis model group; atorvastatin (10mg/kg)-treated group; atorvastatin (20mg/kg)-treated group; atorvastatin (40mg/kg)-treated group. Rats in model group and atorvastatin-treated groups were instilled with bleomycin in trachea (5 mg/kg), and rats in normal group were instilled with equal normal saline; rats in atorvastatin-treated groups were lavaged with different doses of atorvastatin each day from the second day after instillation, and rats in non-atorvastatin-treated groups were lavaged with normal saline. Five rats in each group were chosen randomly on the 1st week,2nd week and 4th week after bleomycin instillation, and the blood was drawn from abdominal aorta to test blood gas analysis and lung tissue samples were harvested for histopathology study. The extent of alveolus inflammation and pulmonary fibrosis was determined by HE and Masson staining respectively and the protein levels of TGF-β1 and CTGF in pulmonary tissues were determined by histoimmunochemical stain.ResultsFrom the HE and Masson staining we found that the extent of alveolus inflammation was the strongest one week after bleomycin instillation and earlier pulmonary fibrosis was found two weeks after bleomycin instillation, then typical pulmonary fibrosis example was established successfully four weeks after bleomycin instillation. The arterial partial pressure of oxygenare (PaO2) of rats steped up gradually with the increase of therapeutic dose at each time point and steped up with the prolongation of time in the same group. The protein levels of TGF-β1 and CTGF in pulmonary tissues decreased gradually with the prolongation of time. The expression of TGF-β1 and CTGF were significantly lower in atorvastatin-treated groups than that in modle group at each time point. The more doses of therapeutic, the less expression of TGF-β1 and CTGF. There was significent difference between each group (P<0.05).ConclusionsThe modle of pulmonary fibrosis of rats can be established successfully by the method of instilling bleomycin in trachea through oral trachea cannula one time. Both TGF-β1 and CTGF play important role in the development of pulmonary fibrosis, and the expressions of TGF-β1 and CTGF are in remarkable positive correlation. The therapeutic effect of atorvastatin on bleomycin-induced pulmonary fibrosis of rats is remarkable, which is dependent on the dose and course of treatment.