[Renoprotective effects of nonselective endothelin receptor antagonist bosentan on rats with interstitial fibrosis following unilateral ureteral obstruction].
OBJECTIVE
To investigate the effects of nonselective endothelin receptor antagonist bosentan on the progression of renal interstitial fibrosis following unilateral ureteral obstruction (UUO).


METHODS
Eighteen female SD rats were randomly divided into 3 groups: intervention group (administered with bosentan for 7 days after left ureter ligation), animal model group (administered with solution of Arabic gum for 7 days left ureter ligation) and sham operation group (administered with Arabic gum for 7 days after sham operation). Seven days after the operation the rats were killed and their left kidneys were harvested. The mRNA expressions of preproendothelin-1 (prepro ET-1), type I collagen (ColI), transforming growth factor beta1 (TGF-beta1), tissue inhibitors of metalloproteinase-1 (TIMP-1) and type 1 plasminogen activator inhibitor (PAI-1) were detected semiquantitatively with reverse transcription-polymerase chain reaction (RT-PCR). The protein expressions of endothelin-1 (ET-1), ColI, TGF-beta1, TIMP-1 and PAI-1were determined semiquantitatively by immunohistochemical staining assay.


RESULTS
The mRNA expressions of prepro ET-1, ColI, TGF-beta1, TIMP-1 and PAI-1 were significantly upregulated in obstructed renal tissue compared to those in sham operation group (all P < 0.05). The positive staining areas of ET-1, ColI, TGF-beta1, TIMP-1 and PAI-1 in tubulointerstitium were markedly enhanced in the animal model group in comparison with those in the sham operation group (all P < 0.05). The mRNA expressions of ColI, TGF-beta1 and TIMP-1 in renal tissue subjected to ureter ligation were significantly lower in the bosentan group then in the animal model group (all P < 0.05). The positive staining areas of ColI, TGF-beta1 and TIMP-1 in the tubulointerstitium were significantly smaller in bosentan group than in the animal model group (all P < 0.05). However, there was no significant difference in the mRNA expression of PAI-1 and in the positive staining area between the animal model group and bosentan group (both P > 0.05).


CONCLUSIONS
ET-1 may be involved in the progression of renal interstitial fibrosis following unilateral ureter ligation and blockage of its receptors with bosentan attenuates the fibroticlesion to a certain extent by possibly inhibiting TGF-beta1 and TIMP-1.
Tian
Xue-fei
XF
Division of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China.
Tang
Gong-yao
GY
Chen
Yi-pu
YP
D000818:Animals; D000077300:Bosentan; D024042:Collagen Type I / Q000032:analysis; D019332:Endothelin-1 / Q000032:analysis / Q000502:physiology; D005260:Female; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D014517:Ureteral Obstruction / Q000150:complications*
D024042:Collagen Type I; D019332:Endothelin-1; D020011:Protective Agents; D013449:Sulfonamides; D019715:Tissue Inhibitor of Metalloproteinase-1; D000077300:Bosentan