Date Published: February 28, 2019
Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em
Author(s): Guangming Zhang, Guanghua Cui, Shuangxi Tong, Qingxian Cao.
To investigate the protective effects of salvianolic acid A (SAA) on renal
damage in rats with chronic renal failure (CRF).
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.
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). 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.
Chronic renal failure (CRF) is a kind of clinical disease in which the basic renal
function cannot be maintained due to various causes of renal parenchymal damage and
atrophy. The main clinical symptoms of CRF are the retention of metabolites,
imbalance of water and electrolyte, acid-base imbalance and systemic involvement.
CRF is the ultimate stage of the development of various chronic kidney diseases1. Renal interstitial fibrosis is a common pathological change of many chronic
kidney diseases which eventually evolve into CRF2. The main manifestation of renal interstitial fibrosis is the high
expression of transforming growth factor-β1 (TGF-β1)3. Smad protein is the key factors in the transduction of TGF-β1 family signal
from receptor to nucleus4. Bone morphogenetic protein 7 (BMP-7) is an important anti-renal
interstitial fibrosis factor influencing the signal transduction of TGF-β1/Smads
pathway and reversing with TGF-β15. Salvianolic acid A (SAA) is a water-soluble phenolic acid compound in the
dried roots and rhizomes of Salvia miltiorrhiza Bunge.
Pharmacological studies have confirmed that, SAA has significant anti-oxidative6, myocardial ischemia protective7, anti-thrombosis8, and anti-hepatic fibrosis effect9. Salvia miltiorrhiza Bunge has been widely used in the
treatment of chronic kidney disease, and its anti-fibrosis effect has been
recognized by the majority of physicians10. Zhang et al.11 have reported that, SAA can attenuates kidney injury in 5/6Nx rats, which is
attributed to its anti-inflammatory activities through inhibition of the activation
of the NF-κB and p38 MAPK signaling pathways. In Li et al.12, SAA may protect the renal function and improve the tubular function and
renal pathology in rats with unilateral ureteral obstruction, which may be related
to a reduction in inflammatory cytokines CCL5 and CXCL10 secretion. Are there any
other mechanisms? In the present study, we observed the protective effect of SAA on
the renal damage in rats with CRF and further discussed the underlying mechanisms,
for providing an experimental basis for the clinical application of SAA to treatment
This study was approved by the Animals Research Ethics Committee of the Affiliated
Hospital of Beihua University. All animal procedures were in accordance with the
Guide for the Care and Use of Laboratory Animals by the National Institutes of
In the present study, the CRF model of rats was established, and the effect of SAA
on the renal damage in CRF rats were investigated. The result showed that, after CRF
modeling, compared with group S, in groups CRF the body weight of rats was
increased, the BUN and Scr levels were increased, and the Ccr level was decreased.
This suggests that, there is obvious renal damage in CRF rats. After treatment,
compared with group CRF, in group CRF+SAA the body weight was increased, the Scr and
BUN levels were decreased, and the Ccr level was increased. This suggests that, SAA
can alleviate the renal damage in CRF rats.
Salvianolic acid A can alleviate the renal damage in CRF rats. The mechanism may be
related to the anti-oxidative stress, down-regulation of TGF-β1 expression and
up-regulation of BMP-7 and Smad6 expressions in renal tissue.