[Effect of tetramethylpyrazine on expression of Smad7 and SnoN in rats with UUO].
OBJECTIVE
To study effect and mechanisms of tetramethylpyrazine (TMP) on renal interstitial fibrosis induced by unilateral ureteral obstruction in rats.


METHODS
Eighteen male Sprague-Dawley rats were randomly divided into sham-operated group, model group and TMP group, 6 in each group. The model of renal interstitial fibrosisi was established in rats by unilateral ureteral obstruction. All rats were killed at the end of the 3rd week after treatment. Pathological change and collagen deposition of the kidneys in rats were observed with HE staining and Masson's collagen staining, respectively. The contents of procollagen III N-terminal peptide and TGF-beta 1 in renal tissue homogenates were tested by radioimmunoassay and ELISA, respective. Protein expression levels of Smad 7 and the Smad transcriptional corepressors SnoN in the obstructed kidney were analyzed by Western blotting.


RESULTS
Pathological examination of the kidneys in the model group showed renal tubule atrophied and lumens expanded, tubular interstitium broadened, large amount of collagen interstitial deposited. The contents of procollagen III N-terminal peptide and TGF-beta 1 were higher and the protein expression levels of Smad7 and SnoN were significantly lower than those in the sham-operated group. Compared with the model group, TMP ameliorated the pathological lesion of the obstructed kidney, decreased the procollagen III N-terminal peptide and TGF-beta 1 contents, significantly increased the expression levels of Smad7 and SnoN protein.


CONCLUSIONS
TMP can evidently resist renal interstitial fibrosis induced by UUO in rats, which might be related with down-regulation of the contents of TGF-beta 1, which is a potent profibrosis cytokine, meanwhile up-regulation of the protein expression levels of Smad7 and SnoN in renal tissue.
Lu
Min
M
Scientific Experimental Center of Shanghai Traditional Chinese Medicine University, Shanghai 201203, China.
Zhou
Juan
J
Wang
Fei
F
Liu
Yumin
Y
Zhang
Yue
Y
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D051906:Smad7 Protein / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011347:Procollagen; D011719:Pyrazines; C511209:Skil_v1 protein, rat; D051906:Smad7 Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C093212:procollagen type II carboxy-terminal peptide; D003094:Collagen; C017953:tetramethylpyrazine