[Dynamic observation of enalapril on the expression of TGF-beta1, CTGF, Smad7 and alpha-SMA in rats with unilateral ureteral obstruction].
OBJECTIVE
To dynamically observe the effect of enalapril on the expression of transforming growth factor beta1 (TGF-beta1), connective tissue growth factor (CTGF), alpha-smooth muscle actin (alpha-SMA), and Smad7 in the obstructed kidney after unilateral ureteral obstruction (UUO) in rats, and to investigate the effect of enalapril on transdifferentiation of renal tubular epithelial cells.


METHODS
The model rats were induced by ligating the left ureter. Male Sprague-Dawley (SD) rats were divided into a normal control (sham-surgery) group, a model group, and a treatment group (enalapril 10 mg/ (kg * d) by gastric gavage from 24 h before the obstruction day). Rats were sacrificed on day 3, 7, 14, 21 after UUO was initiated. Sections of the renal tissue were stained with hematoxylin and eosin stain, which were used for histological and morphometric studies of the pathological change of the obstructed kidney. Real-time PCR was performed to examine the expression of TGF-beta1 mRNA and CTGF mRNA, and Western blot was performed to examine the expression of Smad7, alpha-SMA, and CTGF in the obstructed kidney.


RESULTS
The score of renal interstitial lesion increased with the extension of obstruction. The expression of TGF-beta1 mRNA, CTGF mRNA, alpha-SMA and CTGF increased in the model group with the extension of obstruction; but Smad7 expression decreased. Compared with the UUO group,the degree of renal interstitial lesion and the expression of TGF-beta1 mRNA, CTGF mRNA, alpha-SMA and CTGF were decreased, but the expression of Smad7 increased in the treatment group. Enalapril could significantly decrease TGF-beta1 mRNA on day 3, 7, 14, 21 after UUO. Enalapril could significantly affect the expression of CTGF mRNA,alpha-SMA,CTGF and Smad7 on day 3, 7, 14 after UUO initiation.


CONCLUSIONS
Enalapril significantly alleviates renal interstitial fibrosis by suppressing the expression of TGF-beta1, CTGF and alpha-SMA, upregulating the expression of Smad7, and has better effect at early stage (within 14 days after the UUO).
Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, China.
Linna
L
Wang
Wangbin
W
Ning
Lijian
L
Tao
Ling
L
Wang
Zhangzhe
Z
Peng
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D004656:Enalapril / Q000627:therapeutic use*; D005355:Fibrosis / Q000517:prevention & control; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000199:Actins; D000806:Angiotensin-Converting Enzyme Inhibitors; D055513:Connective Tissue Growth Factor; D004656:Enalapril; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; C526316:CCN2 protein, rat; C497808:Smad7 protein, rat; C498862:Acta2 protein, rat