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[The renal protective effect of selective cyclooxygenase-2 inhibitor on obstructive nephropathy]
1Division of Nephrology, Hua Shan Hospital, Fu Dan University, Shanghai 200040, China.
Objective:
To observe the effect of selective cyclooxygenase-2 (COX-2) inhibitor-meloxicam on the progression of tubulointerstitial fibrosis in rats with unilateral ureteral obstruction (UUO).
Methods:
UUO rats were treated with meloxicam (M), indomethacin (I) or vehicle alone (U) for 4 weeks. Using reverse transcription-polymerase chain reaction (RT-PCR), we examined the mRNA expressions of transforming growth factor (TGF)-beta receptor-1 and 2 in left kidney from rats with UUO. Immuno-precipitation and immunohistochemistry analysis were carried out to investigate the protein level of TGF-beta(1). Tubulointerstitial fibrosis was quantified by Masson's staining. Similar studies were performed in another group of rats with sham operation (C).
Results:
mRNA expressions of TGF-beta receptor-1 and 2 were markedly increased in Group U compared with those in Group C. Both meloxicam and indomethacin inhibited their expressions to a different degree (P < 0.01), but the effect of meloxicam was more significant. Meloxicam decreased the protein level of TGF-beta(1) (P < 0.01), while indomethacin had no such effect. Compared with Group C, there appeared tubulointerstitial fibrosis in the kidney of rats with UUO. The lesion was aggravated by indomethacin, but remarkably attenuated by meloxicam.
Conclusions:
In summary, selective COX-2 inhibitor-meloxicam has a salutary effect on the tubular and interstitial response to UUO. TGF-beta and its receptor approaches partly explain some of the mechanism.