[Experimental study in renal protective effect of tranilast on rats with adriamycin nephropathy].
OBJECTIVE
To investigate the effect and mechanism of tranilast on the adriamycin-induced nephrotic syndrome of rats.


METHODS
Twenty four rats were randomly divided into 4 groups: normal control group, model group, irbesartan treatment group and tranilast treatment group. The rats in normal control group were injected with normal saline via the tail vein. The rats in the other groups were uninephrectomized and injected with adriamycin 5 mg/kg via the tail vein one week later. Rats in model group underwent gavage to receive the sodium carboxymethylcellulose, rats in irbesartan treatment group to receive the irbesartan with 10 mg/kg x d, and rats in tranilast treatment group to receive the tranilast with 400 mg/kg. Rats were then sacrificed at the end of week 8. The body weight, 24 hours urinary protein, blood urea nitrogen (BUN) and serum creatinine (Scr) of each group rats were measured for the study. Renal pathological changes were evaluated. And immunohistochemistry was used to examine the expression of transforming growth factor beta1 (TGF-beta1) and tissue inhibitor of metalloproteinase 1 (TIMP-1). In situ hybridization was used to measure the expression of a-smooth muscle actin (alpha-SMA) mRNA in the kidney.


RESULTS
Compared with the untreated nephrotic syndrome rats, the proteinuria and Scr of rats treated with tranilast were significantly reduced (P < 0.05); Compared with model group, the renal pathological changes of rats in tranilast treatment group were decreased, with glomerular sclerosis to be markedly lower; Tranilast could decrease the expression of TGF-beta1, TIMP-1 and alpha-SMA mRNA in the kidney of rats with adriamycin nephropathy.


CONCLUSIONS
Tranilast has a renoprotective effect on adriamycin-induced nephrotic syndrome in rats, of which the mechanism may be related to that tranilast can depress the expression of TGF-beta1, and TIMP-1 in the kidney, with result in decreasing the synthesis and secretion of extracellular matrix. And tranilast inhibits the transdifferentation of renal primary cells, regulates the synthesis and degradation system of extracellular matrix.
Tao
Ye
Y
Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China.
Wu
Xin
X
Li
Dan-dan
DD
Liu
Qi-feng
QF
Bo
Hong
H
Wang
Xue-rong
XR
D000199:Actins / Q000378:metabolism; D000818:Animals; D004317:Doxorubicin / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D009404:Nephrotic Syndrome / Q000378:metabolism* / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology; D011507:Proteinuria / Q000473:pathology; D051381:Rats; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000199:Actins; D004317:Doxorubicin; D020011:Protective Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D062367:ortho-Aminobenzoates; C498862:Acta2 protein, rat; C012293:tranilast