Effect of large dose of losartan on tubulointerstitial inflammation and fibrosis in rat unilateral ureteral obstruction model / 中华肾脏病杂志

ABSTRACT

Objective To investigate the effect of losartan on tubulointerstitial fibrosis of rat unilateral ureteral obstruction(UUO) model, and to study whether the use of large dose could be better exert a superior renoprotective effect than conventional dose. Methods Three days after UUO, rats were randomly assigned to conventional dose and large dose of losartan group, shamoperated group and operation group. Two treatment groups were administered orally with a daily dose of losartan 50 mg/kg or 500 mg/kg by gastric gavage. Sham-operated group and operation group received the same volume of physiological saline. Rats were sacrificed 7, 14, 21 days after obstruction. Daily urinary albumin excretion(UalbV), tail-cuff pressure(TCP), the percentage of renal tubular lesions, fractional interstitial area (INT), macrophage infiltration and the expression of transforming growth factor (TGF)-β1 mRNA were assessed and compared. Results The TCP, UalbV, percentage of tubular lesions and interstitial fibrosis, the number of interstitial macrophages and the expression of TGF-β1 mRNA were significantly increased in operation group as compared with other groups (P<0.05). Furthermore, in comparison with conventional dose, the large dose treatment significantly reduced TCP and UalbV, attenuated interstitial fibrosis and tubular lesions, suppressed macrophages infiltration and the expression of TGF-β1 mRNA. Conclusion The large dose of losartan provides superior renoprotection compared to the treatment with conventional dose in UUO model, which interrupts the positive feedback involved in the vicious cycle between inflammatory cell and Ang Ⅱ.