The effects of atorvastatin on paraquat-induced pulmonary fibrosis and its mechanism

To evaluate the effects of atorvastatin on paraquat(PQ)-induced pulmonary fibrosis,we investigated atorvastatin-induced changes of matrix metal proteinases expression in pulmonary tissue fibroblasts of rats with acute paraquat poisoning.Total of 105 SD rats were randomly divided into control group,PQ poisoned group,and atorvastatin group.The rats in PQ group and atorvastatin group were treated intragastrically with PQ(50 mg/kg),while the rats in control group were treated with the same dose of distilled water at the beginning of the experiment.Then the atorvastatin group received atorvastatin [1.5 mg/(kg·d)] administration and the other two groups received saline.At day 7,14,and 21,rats were sacrificed and pulmonary interstitial fibroblasts were separated and extracted to evaluate the expressions of MMP-2,MMP-9,and TGF-β1,the lung index,and the pathological changes in lung tissue.We found that in atorvastatin group,MMP-2,MMP-9,TGF-β1,hydroxyproline(HYP),lung index were significantly reduced(P0.05),as compared with paraquat poisoning group.Pathologic examination found that in paraquat group,normal alveolar structure disappeared,inflammatory cell permeated,fibroblast proliferated,and alveolar septum was obviously enlarged,with patchy collagen deposition and changes to fibrosis;while in atorvastatin group,fewer inflammatory cells penetrated,a small amount of fibroblasts found,collagen deposition and more normal lung tissue observed,and lung injury was significantly reduced as compared with paraquat group.According to above results,we concluded that atorvastatin can inhibit the expression of MMP-2,MMP-9,TGF-β1,and HYP,thus significantly reduce pulmonary fibrosis.