Abstract:

Objective To observe the progression of renal tubulointerstitial fibrosis in rat unilateral ureteral obstruction (UUO) models, and investigate the changes in expression of renal fibrosis-related proteins during the pathological course. Methods Thirty-two SD rats were randomly divided into sham-operation group (n=16) and UUO model group (model group, n=16). Rats were sacrificed 2, 5, 9 and 14 d after operation (after model establishment for model group) (n=4 for each day), and the renal tissues of the operated side (obstructed side for model group) were obtained. HE staining, Masson staining, immunohistochemical staining and Western blotting were used to evaluate the degree of renal tubulointerstitial fibrosis and detect the expression of α-smooth muscle actin (α-SMA), fibronectin (FN), vitamin D receptor (VDR) and transforming growth factor-β1 (TGF-β1) in renal tissues. Results Histological observations of renal tissues revealed that the degree of renal tubulointerstitial fibrosis gradually increased with time of ureteral obstruction. It was indicated by immunohistochemical staining that the percentages of area with positive α-SMA and FN in renal interstitium of model group, which gradually increased with time of ureteral obstruction and reached the peak 14 d after model establishment, were significantly higher than those of sham-operation group at each time point after model establishment (P<0.05). Western blotting analysis demonstrated that the relative expression of α-SMA and TGF-β1 at each time point after model establishment in model group was significantly higher than that in sham-operation group (P<0.05), while the relative expression of VDR was significantly lower than that in sham-operation group (P<0.05). The relative expression of α-SMA in renal tissues of rats in model group significantly increased on the second day after model establishment, and the relative expression of α-SMA and TGF-β1 in model group was 12.7 times and 8.8 times respectively of that in sham-operation group on the fourteenth day after model establishment, while the relative expression of VDR decreased to 3% of sham-operation group. Conclusion Significant interstitial fibrosis may emerge at 14 d after model establishment in rat UUO models.The expression of α-SMA in renal interstitium increases in the early stage of model establishment, indicating the activation of renal interstitial fibroblasts. The progression of decrease in expression of VDR indicates VDR may relate to renal interstitial fibrosis.

Key words: renal tubulointerstitial fibrosis, unilateral ureteral obstruction, α-smooth muscle actin, vitamin D receptor, transforming growth factor-β1