RESUMO
Abstract Purpose: To investigate the protective effects of salvianolic acid A (SAA) on renal damage in rats with chronic renal failure (CRF). Methods: The five-sixth nephrectomy model of CRF was successfully established in group CRF (10 rats) and group CRF+SAA (10 rats). Ten rats were selected as sham-operated group (group S), in which only the capsules of both kidneys were removed. The rats in group CRF+SAA were intragastrically administrated with 10 mg/kg SAA for 8 weeks. The blood urine nitrogen (BUN), urine creatinine (Ucr), creatinine clearance rate (Ccr), and serum uperoxide dismutase (SOD) and malondialdehyde (MDA) were tested. The expressions of transforming growth factor-β1 (TGF-β1), bone morphogenetic protein 7 (BMP-7) and Smad6 protein in renal tissue were determined. Results: After treatment, compared with group CRF, in group CRF+SAA the BUN, Scr, serum MDA and kidney/body weight ratio were decreased, the Ccr and serum SOD were increased, the TGF-β1 protein expression level in renal tissue was decreased, and the BMP-7 and Smad6 protein levels were increased (all P < 0.05). Conclusion: SAA can alleviate the renal damage in CRF rats through anti-oxidant stress, down-regulation of TGF-β1 signaling pathway and up-regulation of BMP-7/Smad6 signaling pathway.
Assuntos
Animais , Masculino , Ratos , Ácidos Cafeicos/uso terapêutico , Proteína Smad6/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteína Morfogenética Óssea 7/metabolismo , Falência Renal Crônica/tratamento farmacológico , Lactatos/uso terapêutico , Regulação para Baixo , Regulação para Cima , Ratos Sprague-Dawley , Modelos Animais de Doenças , Falência Renal Crônica/induzido quimicamente , Falência Renal Crônica/metabolismo , Testes de Função Renal , NefrectomiaRESUMO
The inhibitory Smad6 and Smad7 are responsible for cross-talk between TGF-beta/bone morphogenic protein (BMP) signaling and other cellular signaling pathways, as well as negative feedback on their own signaling functions. Although inhibitory Smads are induced by various stimuli, little is known about the stimuli that increase Smad6 transcription, in contrast to Smad7. Here we demonstrate that etoposide, which induces double strand breaks during DNA replication, significantly up-regulates the transcription of the Smad6 gene in CMT-93 mouse intestinal cells by increasing specific DNA binding proteins. In addition, endogenous inhibition of the Smad6 gene by RNAi interference led to transient accumulation of G1 phase cells and reduction in incorporation of bromodeoxyuridine (BrdU). These findings strongly suggest that Smad6 plays a distinct role in the signaling of etoposide-induced DNA damage.