Fuzheng Huayu Formula () prevents rat renal interstitial fibrosis induced by HgCl via antioxidative stress and down-regulation of nuclear factor-kappa B activity.

OBJECTIVE

To investigate the mechanism of action of Fuzheng Huayu Formula (, FZHY) against renal interstitial fibrosis (RIF) relating to oxidative injury and nuclear factor-kappa B (NF-κB) activity.

METHODS

Thirty-two Sprague-Dawley rats were randomly divided into 3 groups: normal group, model group and FZHY treatment group. The RIF model was induced by oral administration of HgCl at a dose of 8 mg/kg body weight once a day for 9 weeks. Meanwhile, rats in FZHY treatment group orally took FZHY at a dose of 4.0 g/kg rat weight for 9 weeks. The content of hydroxyproline (Hyp) and collagen deposition in kidney were observed. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the content of glutathione (GSH) and malondialdehyde (MDA) of kidney were tested. The expressions of inhibitor-κappa B (IκB), phospho-IκB (p-IκB), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-2 (MMP-2) and α-smooth muscle actin (α-SMA) were analyzed by Western blot. α-SMA expression was also observed by immunofluorescent staining. MMP-2 activity was measured by gelatin zymography. NF-κB activation was determined by electrophoretic mobility shift assay.

RESULTS

Renal interstitial fibrosis was induced by HgCl, demonstrated by remarkably increased Hyp contents and excessive collagen deposition in kidney (P<0.01). FZHY significantly inhibited renal interstitial collagen deposition and reduced Hyp content of the HgCl-treated rats (P<0.01). GSH content decreased obviously, and MDA content increased signifificantly in HgCl-treated rats compared with that of normal rats (P<0.01). FZHY significantly increased GSH content and decreased MDA content in the model rats (P<0.01). The expression α-SMA was increased in model rats compared with that of normal rats, FZHY signifificantly decreased its expression (P<0.01). The expressions of p-IκB and TNF-α and MMP-2, MMP-2 activity, and NF-κB activation were increased in model group compared with that in normal group (P<0.01), FZHY signifificantly decreased NF-κB activation, MMP-2 activity and p-IκB and TNF-α expressions (P<0.01).

CONCLUSIONS

FZHY could protect kidney from oxidative injury intoxicated by HgCl, and antagonized oxidative stress-stimulated NF-κB activity through inhibition of IκB phosphorylation in the interstitial fibrotic kidney, these effects importantly contributed to FZHY action mechanism against renal interstitial fifibrosis.