【摘 要】
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Objective:To investigate the mechanism of action of Fuzheng Huayu Formula (扶正化瘀方,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
【机 构】
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Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chin
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Objective:To investigate the mechanism of action of Fuzheng Huayu Formula (扶正化瘀方,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 HgCl2 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-κ appa B (I κ B),phospho-I κ B (p-I κ B),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-κ B activation was determined by electrophoretic mobility shift assay.Results:Renal interstitial fibrosis was induced by HgCl2,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 HgCl2-treated rats (P<0.01).GSH content decreased obviously,and MDA content increased significantly in HgCl2-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 significantly decreased its expression (P<0.01).The expressions of p-I κ B and TNF-α and MMP-2,MMP-2 activity,and NF-κ B activation were increased in model group compared with that in normal group (P<0.01),FZHY significantly decreased NF-κ B activation,MMP-2 activity and p-I κ B and TNF-α expressions (P<0.01).Conclusions:FZHY could protect kidney from oxidative injury intoxicated by HgCl2,and antagonized oxidative stress-stimulated NF-κ B activity through inhibition of I κ B phosphorylation in the interstitial fibrotic kidney,these effects importantly contributed to FZHY action mechanism against renal interstitial fibrosis.
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