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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

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Abstract

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-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 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 signifificantly 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 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 HgCl2, 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.

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Authors and Affiliations

  1. Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Ji-li Yuan, Yan-yan Tao, Qing-lan Wang, Li Shen & Cheng-hai Liu

  2. Shanghai Key Laboratory of Traditional, Chinese Clinical Medicine, Shanghai, 201203, China

    Cheng-hai Liu

  3. E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, Shanghai, 201203, China

    Cheng-hai Liu

Authors
  1. Ji-li Yuan
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  2. Yan-yan Tao
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  3. Qing-lan Wang
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  4. Li Shen
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  5. Cheng-hai Liu
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Corresponding author

Correspondence to Cheng-hai Liu.

Additional information

Supported by the National Natural Science Foundation of China (No. 81270053); the National Science and Technology Major Project (No. 2014ZX10005001) and the International S&T Cooperation Program of China (No. 2014DFA31440); "Three-Year Action Plan" for Development of TCM in Shanghai (No. ZY3-CCCX-2-1003).

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Yuan, Jl., Tao, Yy., Wang, Ql. et al. 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. Chin. J. Integr. Med. 23, 598–604 (2017). https://doi.org/10.1007/s11655-016-2540-z

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  • DOI: https://doi.org/10.1007/s11655-016-2540-z

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