Dehydrocostus lactone ameliorates renal interstitial fibrosis in rats with unilateral ureteral obstruction by inhibiting the TGF-β1/Smad2/3 pathway

Objective  To explore the action mechanism of dehydrocostus lactone (DHL) on renal interstitial fibrosis (RIF) in rats with unilateral ureteral obstruction (UUO).

Methods  Forty-four male SD rats were randomly divided into four groups: the sham surgery group (Sham group), the pure drug intervention group (Sham+DHL group), the experimental group (UUO+Vehicle group), and the DHL treatment group (UUO+DHL group), with 11 rats in each group. The rats underwent sham surgery, sham surgery + DHL 10 mg/(kg·d), UUO modeling + the same volume of solvent, and UUO modeling + DHL 10 mg/(kg·d), respectively. After surgery, DHL or the same volume of solvent was administered by gavage for 14 days starting from day 2 post-surgery. Hematoxylin-eosin (HE) and Masson staining were used to observe the pathological changes in renal tissue. Immunohistochemical staining was performed to detect the expression levels of collagen I, collagen III, and α-smooth muscle actin (α-SMA). Western blotting was used to detect the protein levels of the transforming growth factor (TGF)-β1/Smad2/3 pathway.

Results  Compared with the UUO+Vehicle group, DHL treatment alleviated renal interstitial pathological damage, reduced collagen fiber deposition, and decreased the expression of collagen I, collagen III, and α-SMA. It also inhibited the expression of TGF-β1 and Smad2/3 proteins.

Conclusions DHL mitigates RIF in rats by inhibiting the TGF-β1/Smad2/3 pathway, providing a new strategy for the treatment of chronic kidney disease.