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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 40 Issue 4
Apr.  2024
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Article Navigation >  Journal of Clinical Hepatology  > 2024  >  40(4): 745-752

Effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in a mouse model of liver cirrhosis

DOI: 10.12449/JCH240417
  • 1.

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

  • 2.

    Department of Integrated Traditional Chinese and Western Medicine and Liver Diseases，Ningbo Hwa Mei Hospital，University of Chinese Academy of Sciences，Ningbo，Zhejiang 315010，China

  • 3.

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

  • 4.

    Shanghai Pudong New Area Gongli Hospital，Shanghai 200120，China

  • 5.

    Key Laboratory of Liver and Kidney Diseases，Ministry of Education，Shanghai 201203，China

Research funding:

General Project of National Natural Science Foundation of China (82274305)

More Information
  • Corresponding author: LI Zhengxin， zhengxinli1990@hotmail.com （ORCID： 0000-0002-2497-6951）; LIU Chenghai， chenghai.liu@outlook.com （ORCID： 0000-0002-1696-6008）
  • Received Date: 2023-03-02
  • Accepted Date: 2023-06-21
  • Published Date: 2024-04-25
    Abstract
  •   Objective  To investigate the effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in fibrotic liver and its mechanism of action in promoting hepatocyte regeneration.  Methods  Mice were given intraperitoneal injection of CCl4 for 6 weeks to establish a model of liver cirrhosis， and there were 10 mice in the model group， 10 in the sorafenib group， 10 in the Fuzheng Huayu prescription group， and 9 in the normal control group. Since week 4 of modeling， the mice in the Fuzheng Huayu prescription group and the sorafenib group were given the corresponding drug by gavage at a dose of 4.8 g/kg and 4 mg/kg， respectively， for three consecutive weeks， and those in the normal group and the model group were given an equal volume of sodium carboxymethyl cellulose. Serum liver function parameters were measured； the METAVIR scoring system was used to evaluate liver inflammation and fibrosis stage； Sirius Red staining and hydroxyproline （Hyp） content in liver tissue were used to evaluate collagen deposition； immunohistochemistry was used to measure the protein expression levels of type IV collagen， CD31， CD32b， Ki67， CyclinD1， glutamine synthetase， Wnt2， and HGF， and Western blot was used to measure the expression levels of Wnt2， LRP6， β-catenin， p-β-catenin， and CyclinD1 in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups.  Results  Compared with the model group， the Fuzheng Huayu prescription group and the sorafenib group showed the following changes： significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of Hyp in liver tissue （all P<0.01）； a significant reduction in METAVIR score； significant reductions in the expression levels of type Ⅳ collagen and CD31 （all P<0.05） and a significant increase in the expression level of CD32b （P<0.01）； significant reductions in the number of parenchymal extinction lesions and significant increases in the expression levels of Ki67 and CyclinD1 in liver tissue （all P<0.01）； significant increases in the protein expression levels of Wnt2， LRP6， β-catenin， and CyclinD1 and a significant reduction in the protein expression level of p-β-catenin （all P<0.05）； significant increases in the number of cells stained positive for both CD32b and Wnt2.  Conclusion  Fuzheng Huayu prescription can inhibit hepatic sinusoidal capillarization， improve the Wnt2 exocrine function of liver sinusoidal endothelial cells， activate the Wnt/β-catenin signaling pathway associated with hepatocyte regeneration， and finally reverse liver cirrhosis.

     

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