Celecoxib Suppresses the Expression of Connective Tissue Growth Factor by up-regulating cAMP in Rats with Unilateral Ureteral Obstruction Model
- VernacularTitle:塞来昔布上调梗阻肾cAMP水平抑制结缔组织生长因子的表达
- Author:
Houqin XIAO
;
Jiane ZHANG
;
Guohua DING
- Publication Type:Journal Article
- Keywords:
Cyclooxygenase-2;
Trsforming growth factor -beta1;
Connective tissue growth factor;
Celecoxib
- From:
Journal of Chinese Physician
2001;0(09):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the regulation of cyclooxygenase-2 expression and mechanism of selective cyclooxygenase-2 inhibitor Celecoxib suppressing tubulointerstitial fibrosis of rats with unilateral ureteral obstruction(UUO) model. Methods The UUO models were induced by ligating the left ureter. Rats were randomly divided into bulofen group (group B), Celecoxib group (group R), model group (group C) and sham operation group (group S). Rats in group B were given bulofen 300mg?Kg~ -1?d~ -1, and in group R were given Celecoxib 10mg?Kg~ -1?d~ -1 by gastric gavage from 24 h before the obstruction to 14 days after the induction. Rats were sacrificed at 3d, 6d and 14d in batch after the UUO models were induced. The mRNA expressions of cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), transforming growth factor-beta 1 (TGF-?1), and connective tissue growth factor (CTGF) were detected by RT-PCR. The protein expressions of TGF-?1, CTGF and ?-SMA were detected using immunohistochemistry and the content of cAMP was determined by radioimmuno-assay. Results Compared with group S, the mRNA expressions of COX-2, TGF-?1 and CTGF in group C increased markedly after UUO treatment, and the content of cAMP decreased. It showed no significant difference in the mRNA expressions of TGF-?1, CTGF and the content of cAMP for the Bulofen treatment in the UUO model. With the Celecoxib treatment, there was no significant difference on the mRNA expression of TGF-?1, but the content of cAMP increased and the expression of CTGF decreased. Conclusion The COX-2 plays an important role in lesion of tubulointerstitial. Selective cyclooxygenase-2 inhibitor can partially up-regulate the content of cAMP and down-regulate the expression of CTGF, the downstream factor of TGF-?1, which may postpone the renal interstitial fibrosis.
