Fuzheng Huayu Formula（扶正化瘀方） Prevents Rat Renal Interstitial Fibrosis Induced by HgCl2 via Antioxidative Stress and Down-regulation of Nuclear Factor-Kappa B Activity

• Published in: 中国结合医学杂志：英文版 Vol. 23; no. 8; pp. 598 - 604
• Main Author: YUAN Ji-li TAO Yan-yan WANG Qing-lan SHEN Li LIU Cheng-hai
• Format: Journal Article
• Language: English
• Published: 2017
• Subjects: SD大鼠; 扶正; 核因子-κB; 氧化应激; 氯化汞; 活性; 肾间质纤维化; 谷胱甘肽过氧化物酶
• ISSN: 1672-0415; 1993-0402

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 HgC l2 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 of4.0 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）andα-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 Hg Cl2,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 Hg Cl2-treated rats（P〈0.01）.GSH content decreased obviously,and MDA content increased significantly in HgC l2-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 expressionα-SMA was increased in model rats compared with that of normal rats,FZHY significantly decreased its expression（P〈0.01）.The expressions of p-IκB and TNF-αand MMP-2,MMP-2 activity,and NF-κB activation were increased in model group compared with that in normal group（P〈0.01）,FZHY significantly decreased NF-κB activation,MMP-2 activity and p-IκB and TNF-αexpressions（P〈0.01）.Conclusions：FZHY could protect kidney from oxidative injury intoxicated by Hg Cl2,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 fibrosis.