[Effect of Kangxianling on Smads signal pathway molecules in rats with adriamycin induced nephropathy].

OBJECTIVE: To study the effect and mechanism of Kangxianling (KXL, a Chinese compound recipe) in treating adriamycin (ADR) induced renal fibrosis rats.

METHODS: Forty-five male SD rats were randomly divided into 4 groups, the normal group (n = 7), the sham operative group (n = 8), the model group (n = 15), and the treatment group (n = 15). Model of renal interstitial fibrosis was established in rats by unilateral nephrectomy and intravenous injection of ADR twice at a 30-day interval, and the rats in the treatment group treated with KXL once a day for 72 days. Body weight, serum creatinine (SCr), blood urea nitrogen (BUN) levels and endogenous creatinine clearance rate (CCr) of animals were analyzed at the end of the 4th and the 8th week after operation. Rats were sacrificed after 72 days of treatment and their kidney obtained for pathological examination with HE and PASM staining. And protein expression levels of transforming growth factor beta (TGF-beta) receptor I (TbetaR I), TGF-beta receptor II (TbetaR II), Smad2 and Smad7 were determined by Western blotting.

RESULTS: Levels of SCr and BUN in animals of the model group were significantly higher and CCr lower than those in the normal group (P < 0.05). Pathological examination of kidney in the model group showed thickened glomerular/tubular basement membrane with segmental sclerosis and hyaline degeneration; atrophy of the renal tubule around the sclerotic glomeruli and part of them disappeared; hypertrophy of partial glomeruli with surrounding severe dilated tubules; obvious glomeruli centering phenomena; severe tubular epithelial cell degeneration, necrosis with protein cast; fibrous tissue proliferation and large amount of inflammatory cell interstitial infiltration. The protein expression of TbetaR I and Smad2 in kidney tissue of the model group were significantly up-regulated, while that of TbetaR II and Smad7 unchanged. After KXL intervention, level of BUN lowered, SCr tended to normal and the endogenous SCr was raised to some degree. The renal pathological status in the treatment group was significantly improved and with markedly lowering of TbetaR I and Smad2 protein expression.

CONCLUSION: KXL could inhibit the protein expression of TbetaR I and Smad2 in kidney tissue, so as to alleviate the renal fibrosis induced by adriamycin and improve the renal function.