Abstract:

To investigate the effects of pirfenidone (PFD) on liver fibrosis in experimental rats. MethodsFortyfive male Wistar rats were randomly divided into three groups. The model group was intraperitoneally injected with 1% dimethylnitrosamine (DMN) 10?mg/kg per day for the first three days of each week for 4 weeks. The intervention group was orally given PFD 500?mg/kg every day for 4 weeks starting on the day of the first injection of DMN. The control group was given normal sodium. Rats were killed at the end of the 4th week, and the livers and spleens were removed. Blood samples were obtained immediately before rats were killed. Liver histological and ultramicroscopic changes were observed, serum indices of liver fibrosis and liver function were examined, and the level of transforming growth factor β1 (TGFβ1) was determined. ResultsCompared with the model group, the intervention group had a higher bodyweight(P＜0.05) but splenohepatomegalia was less(P＜0.05). Serum levels of hyaluronic acid, laminin and type Ⅳ collagen of the intervention group were significantly lower than those of the model group(P＜0.05), however serum levels of alanine aminotransferase(ALT), aspartate aminotransferase (AST), total bilirubin（TBIL） and TGFβ1 were significantly higher than those of the model group(P＜0.001). Masson trichrome staining showed that the intervention group had mild bridging fibrosis and less lymphocyte infiltration. No typical pseudolobule was found. Transmission electron microscopy demonstrated that hepatic cell injury in the intervention group was significantly less than that in the model group and slight collagen fibers were observed in the sinus hepaticus and Disse space. ConclusionsPFD has a significant antifibrosis effect in experimental rats, which was presumably caused by inhibiting the production of TGFβ1.

Key words: Pirfenidone; Fibrosis, liver; Wistar rats; transforming growth factor β1