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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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    • References(24)
  • [1]
    XU XY, DING HG, LI WG, et al. Chinese guidelines on the management of liver cirrhosis[J]. J Clin Hepatol, 2019, 35( 11): 2408- 2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006.

    徐小元, 丁惠国, 李文刚, 等. 肝硬化诊治指南[J]. 临床肝胆病杂志, 2019, 35( 11): 2408- 2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006.
    [2]
    MAGDALENO F, TREBICKA J. Selective LOXL2 inhibition: potent antifibrotic effects in ongoing fibrosis and fibrosis regression[J]. Gut, 2017, 66( 9): 1540- 1541. DOI: 10.1136/gutjnl-2016-313621.
    [3]
    HARRISON SA, ABDELMALEK MF, CALDWELL S, et al. Simtuzumab is ineffective for patients with bridging fibrosis or compensated cirrhosis caused by nonalcoholic steatohepatitis[J]. Gastroenterology, 2018, 155( 4): 1140- 1153. DOI: 10.1053/j.gastro. 2018.07.006.
    [4]
    QI JS, HU XD, LIU CH. Reversal mechanism of hepatic fibrosis[J]. Chin J Hepatol, 2022, 30( 6): 577- 582. DOI: 10.3760/cma.j.cn501113-20220504-00239.

    齐婧姝, 胡旭东, 刘成海. 肝纤维化的逆转机制[J]. 中华肝脏病杂志, 2022, 30( 6): 577- 582. DOI: 10.3760/cma.j.cn501113-20220504-00239.
    [5]
    LIU CH, ZHAO ZM, LYU J, et al. Advances in the understanding and treatment of liver fibrosis in traditional Chinese medicine[J]. J Clin Hepatol, 2019, 35( 4): 728- 733. DOI: 10.3969/j.issn.1001-5256.2019.04.006.

    刘成海, 赵志敏, 吕靖. 中医对肝纤维化逆转的认识与治疗[J]. 临床肝胆病杂志, 2019, 35( 4): 728- 733. DOI: 10.3969/j.issn.1001-5256.2019.04.006.
    [6]
    CHENG Q, LI N, CHEN M, et al. Fuzheng Huayu inhibits carbon tetrachloride-induced liver fibrosis in mice through activating hepatic NK cells[J]. J Ethnopharmacol, 2013, 145( 1): 175- 181. DOI: 10.1016/j.jep.2012.10.047.
    [7]
    PAN Q, WANG YQ, LI GM, et al. Fuzheng Huayu recipe ameliorates liver fibrosis by restoring balance between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition in hepatic stellate cells[J]. Biomed Res Int, 2015, 2015: 935903. DOI: 10.1155/2015/935903.
    [8]
    ZHANG M, LIU HL, HUANG K, et al. Fuzheng Huayu recipe prevented and treated CCl4-induced mice liver fibrosis through regulating polarization and chemotaxis of intrahepatic macrophages via CCL2 and CX3CL1[J]. Evid Based Complement Alternat Med, 2020, 2020: 8591892. DOI: 10.1155/2020/8591892.
    [9]
    LIU HL, LV J, ZHAO ZM, et al. Fuzhenghuayu Decoction ameliorates hepatic fibrosis by attenuating experimental sinusoidal capillarization and liver angiogenesis[J]. Sci Rep, 2019, 9( 1): 18719. DOI: 10.1038/s41598-019-54663-4.
    [10]
    YANG T, SHEN DP, WANG QL, et al. Investigation of the absorbed and metabolized components of Danshen from Fuzheng Huayu recipe and study on the anti-hepatic fibrosis effects of these components[J]. J Ethnopharmacol, 2013, 148( 2): 691- 700. DOI: 10.1016/j.jep.2013.05.031.
    [11]
    JAMALL IS, FINELLI VN, QUE HS. A simple method to determine nanogram levels of 4-hydroxyproline in biological tissues[J]. Anal Biochem, 1981, 12( 1): 70- 75. DOI: 10.1016/0003-2697(81)90261-x.
    [12]
    WANLESS IR, NAKASHIMA E, SHERMAN M. Regression of human cirrhosis. Morphologic features and the genesis of incomplete septal cirrhosis[J]. Arch Pathol Lab Med, 2000, 124( 11): 1599- 607. DOI: 10.5858/2000-124-1599-ROHC.
    [13]
    STUECK AE, WANLESS IR. Hepatocyte buds derived from progenitor cells repopulate regions of parenchymal extinction in human cirrhosis[J]. Hepatology, 2015, 61( 5): 1696- 707. DOI: 10.1002/hep.27706.
    [14]
    WANLESS IR. The role of vascular injury and congestion in the pathogenesis of cirrhosis: the congestive escalator and the parenchymal extinction sequence[J]. Curr Hepatology Rep, 2020, 19: 40- 53. DOI: 10.1007/s11901-020-00508-y.
    [15]
    HYTIROGLOU P, THEISE ND. Regression of human cirrhosis: an update, 18 years after the pioneering article by Wanless et al[J]. Virchows Arch, 2018, 473( 1): 15- 22. DOI: 10.1007/s00428-018-2340-2.
    [16]
    XU XJ, LU LG. Basic and clinical studies on reversal of liver fibrosis after hepatitis C virus eradication[J]. Chin Hepatol, 2021, 26( 8): 840- 842. DOI: 10.3969/j.issn.1008-1704.2021.08.005.

    徐贤军, 陆伦根. 丙型肝炎病毒根除后肝纤维化逆转基础和临床研究[J]. 肝脏, 2021, 26( 8): 840- 842. DOI: 10.3969/j.issn.1008-1704.2021.08.005.
    [17]
    XU Y, ZHANG YG, WANG X, et al. Long-term antiviral efficacy of entecavir and liver histology improvement in Chinese patients with hepatitis B virus-related cirrhosis[J]. World J Gastroenterol, 2015, 21( 25): 7869- 7876. DOI: 10.3748/wjg.v21.i25.7869.
    [18]
    MARCELLIN P, GANE E, BUTI M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study[J]. Lancet, 2013, 381( 9865): 468- 475. DOI: 10.1016/S0140-6736(12)61425-1.
    [19]
    DING BS, NOLAN DJ, BUTLER JM, et al. Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration[J]. Nature, 2010, 468( 7321): 310- 315. DOI: 10.1038/nature09493.
    [20]
    ZHAO L, JIN Y, DONAHUE K, et al. Tissue repair in the mouse liver following acute carbon tetrachloride depends on injury-induced Wnt/β-catenin signaling[J]. Hepatology, 2019, 69( 6): 2623- 2635. DOI: 10.1002/hep.30563.
    [21]
    HU S, MONGA SP. Wnt/β-catenin signaling and liver regeneration: Circuit, biology, and opportunities[J]. Gene Expr, 2021, 20( 3): 189- 199. DOI: 10.3727/105221621X16111780348794.
    [22]
    RUSSELL JO, MONGA SP. Wnt/β-catenin signaling in liver development, homeostasis, and pathobiology[J]. Annu Rev Pathol, 2018, 13: 351- 378. DOI: 10.1146/annurev-pathol-020117-044010.
    [23]
    XU LM, LIU P, SHEN XZ, et al. Guidelines for the diagnosis and treatment of liver fibrosis in integrative medicine practice(2019)[J]. J Clin Hepatol, 2019, 35( 7): 1444- 1449. DOI: 10.3969/j.issn.1001-5256.2019.07.007.

    徐列明, 刘平, 沈锡中, 等. 肝纤维化中西医结合诊疗指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35( 7): 1444- 1449. DOI: 10.3969/j.issn.1001-5256.2019.07.007.
    [24]
    CHENG J, Modern molecular biology of the extracellular matrix·Extracellular matrix and clinical medicine[M]. Beijing: Science Press, 2012: 696- 711.

    成军. 现代细胞外基质分子生物学·细胞外基质与临床医学[M]. 北京: 科学出版社, 2012: 696- 711.
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