Abstract: SA-PO348

The Effect of Hirudin on PAR-1,TGF-β1, α-SMA of Renal Interstitial Tissue in Rats with Unilateral Ureteral Obstruction

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

  • Lu, Dai, Division of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
  • Kang, Yang, Tianjin University of Chinese Traditional Medicine, Tianjin, China
  • Ming, Pei, Division of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
  • Tong, Ren, Division of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
  • Hu, Shouci, Tianjin University of Chinese Traditional Medicine, Tianjin, China
  • Wei, Lijuan, Tianjin University of Chinese Traditional Medicine, Tianjin, China
  • Yang, Bo, Division of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
  • Yan, Lin, Division of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
  • Yang, Hongtao, Division of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
Background

In the process of renal interstitial fibrosis, hirudin may reduce the expression of proteins and genes of PAR-1, TGF-β1 and α-SMA in the renal interstitial, We explored the intervention effect of hirudin by establishing a unilateral ureteral obstruction model.

Methods

The 90 healthy Sprague-Dawley (SD) male rats, with the average weight of 180±20g, were randomly divided into Sham-operation group(SOR,n=18), unilateral ureteral obstruction model group(UUO,n=18), UUO with high dose Hirudin treatment group(UUO+HI,n=18),UUO with low dose Hirudin treatment group(UUO+LI,n=18), UUO with Lotensin treatment group(UUO+LOT,n=18). On 3rd,7th,14th days after the operation, 6 rats from each group were randomly sacrificed, the obstructive side of kidneys were storaged for RT-PCR and Western Blot tests to detected the expression of proteins and genes of PAR-1, TGF-β1, α-SMA with drug intervention.

Results

1 Western Blot test: Compared with UUO group, the expression of PAR-1, TGF-β1 and α-SMA at each time point in UUO+LOT and UUO+HI groups were significantly reduced (P<0.05).
2 RT-PCR test: Compared with UUO group, the expression of PAR-1 and α-SMA at each time points in each intervention groups were reduced (P<0.05). Compared with UUO group, the expression of TGF-β1 at different time points in UUO+HI group, on the 14th day in UUO+LI and UUO+LOT groups were decreased(P<0.05).

Conclusion

High dose of hirudin can significantly reduce the protein expression of PAR-1, TGF-β1 and α-SMA in renal interstitial of UUO rat model. Both high dose and low dose of hirudin can reduce the mRNA expression of PAR-1, TGF-β1, α-SMA in different degrees. Compared with UUO+LI group, UUO+HI group has a better effect on the down-regulation of the protein and mRNA expression of PAR-1, TGF-β1, α-SMA, the difference between two groups may be related to the mechanism of the best drug effective dose.

Funding

  • Government Support - Non-U.S.