Berberine ameliorates renal interstitial fibrosis induced by unilateral ureteral obstruction in rats

Aim: To investigate the potential effects of berberine on renal interstitial fibrosis (RIF) of obstructed kidneys in a unilateral ureteral obstruction (UUO) rat model. Methods: Forty-eight rats were randomly divided into three groups: shamoperated, vehicle-treated UUO, and berberine-treated UUO. Rats were gavaged with berberine (200 mg/kg per day) or vehicle. Eight randomly chosen rats in each group were kiled and specimens were collected at day 14 after UUO. Physiological parameters and histological changes were assessed, RIF was evaluated using Masson's trichrome and Sirius red staining, oxidative stress and inflammation markers were determined, transforming growth factor beta 1 (TGF-beta 1), phosphorylated Smad3 (pSmad3) and alpha-smooth muscle actin (alpha-SMA) were measured using immunohistochemistry or western blotting analysis. The obstruction was relieved at day 14 by percutaneous nephrostomy in the remaining UUO rats. The resistive index of left kidneys was undertaken by coloured Doppler flow imaging at day 14 before nephrostomy and day 7 after the relief. Results: Berberine treatment significantly attenuated RIF induced by UUO. The UUO-induced reduction in kidney superoxide dismutase and catalase activities increased, whereas elevated kidney malondialdehyde level markedly decreased. Berberine treatment significantly ameliorated UUO-induced inflammation, and decreased TGF-beta 1, pSmad3 and alpha-SMA expression of UUO kidneys. Moreover, berberine treatment significantly suppressed the increase of resistive index compared with UUO group at day 14 after UUO as well as day 7 after the relief of obstruction. Conclusion: Berberine treatment ameliorates RIF in a UUO rat model by inhibition of oxidative stress, inflammatory responses, and TGF-beta 1/pSmad3 signalling.