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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 40 Issue 2
Feb.  2024
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Article Navigation >  Journal of Clinical Hepatology  > 2024  >  40(2): 312-318

Protective mechanism of rhubarb decoction against inflammatory damage of brain tissue in rats with mild hepatic encephalopathy： A study based on the PI3K/AKT/mTOR signaling pathway

DOI: 10.12449/JCH240215
  • 1.

    Graduate School of Guangxi University of Chinese Medicine，Nanning 530200，China

  • 2.

    Department of Scientific Research，Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine，Nanning 530011，China

  • 3a.

    Department of Hepatology，The First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530023，China

  • 3b.

    Department of Spleen and Stomach，The First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530023，China

  • 3c.

    Laboratory of Molecular Biology，The First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530023，China

  • 3d.

    Department of Oncology，The First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530023，China

Research funding:

National Natural Science Foundation of China (82260899);

National Natural Science Foundation of China (82060848);

National Natural Science Foundation of China (81804019);

Guangxi Natural Science Foundation Key Project (Gui Ke AB22035076);

Guangxi Natural Science Foundation Project (2020GXNSFAA297070);

Cultivation of Guangxi First-class Disciplines in Integrative Medicine (Gui Ke Research［2018］No.12);

Cultivation of Guangxi First-class Disciplines in Integrative Medicine (2019XK145);

Guangxi Postgraduate Education Innovation Programme Funded Projects (YCSW2022349);

Guangxi Postgraduate Education Innovation Programme Funded Projects (YCSY2023033);

Guangxi Postgraduate Education Innovation Programme Funded Projects (YCSZ2022017)

More Information
  • Corresponding author: MAO Dewen， mdwboshi2005@163.com （ORCID： 0000-0001-9438-9325）; YAO Chun， yaochunlshn@163.com （ORCID： 0000-0003-2903-8814）
  • Received Date: 2023-05-19
  • Accepted Date: 2023-07-04
  • Published Date: 2024-02-19
    Abstract
  •   Objective  To investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）.  Methods  A total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain 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 MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups.  Conclusion  Retention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.

     

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    • References(15)
  • [1]
    Chinese Society of Hepatology, Chinese Medical Association. Guidelines on the management of hepatic encephalopathy in cirrhosis[J]. J Clin Hepatol, 2018, 34( 10): 2076- 2089. DOI: 10.3969/j.issn.1001-5256.2018.10.007.

    中华医学会肝病学分会. 肝硬化肝性脑病诊疗指南[J]. 临床肝胆病杂志, 2018, 34( 10): 2076- 2089. DOI: 10.3969/j.issn.1001-5256.2018.10.007.
    [2]
    HÄUSSINGER D, SCHLIESS F. Pathogenetic mechanisms of hepatic encephalopathy[J]. Gut, 2008, 57( 8): 1156- 1165. DOI: 10.1136/gut.2007.122176.
    [3]
    STARK AK, SRISKANTHARAJAH S, HESSEL EM, et al. PI3K inhibitors in inflammation, autoimmunity and cancer[J]. Curr Opin Pharmacol, 2015, 23: 82- 91. DOI: 10.1016/j.coph.2015.05.017.
    [4]
    NIU YB. Effect of metformin on acute liver injury induced by carbon tetrachloride in mice by inhibiting PI3K-AKT-mTOR signaling pathway[D]. Taiyuan: Shanxi Medical University, 2020.

    牛艳邦. 二甲双胍通过抑制PI3K-AKT-mTOR信号通路对四氯化碳诱导的小鼠急性肝损伤的影响[D]. 太原: 山西医科大学, 2020.
    [5]
    MAO DW, WU JH, QIU H, et al. Theoretical discussion on the treatment of hepatic encephalopathy with the method of”dredging fu organs and inducing resuscitation”[J]. J Sichuan Tradit Chin Med, 2008, 26( 10): 22- 24.

    毛德文, 武建华, 邱华, 等.” 通腑开窍”法治疗肝性脑病的理论探讨[J]. 四川中医, 2008, 26( 10): 22- 24.
    [6]
    YAO C, YAO F, XIE W, et al. Clinical observation on rhubarb decoction retention Enema in treatment of minimal hepatic encephalopathy[J]. Liaoning J Tradit Chin Med, 2013, 40( 3): 474- 476. DOI: 10.13192/j.ljtcm.2013.03.96.yaoch.089.

    姚春, 姚凡, 谢武, 等. 大黄煎剂保留灌肠治疗轻微肝性脑病临床研究[J]. 辽宁中医杂志, 2013, 40( 3): 474- 476. DOI: 10.13192/j.ljtcm.2013.03.96.yaoch.089.
    [7]
    ZHU RH, HUANG JJ, HUANG HN, et al. Mechanism of action of Rheum officinale decoction in treatment of minimal hepatic encephalopathy based on network pharmacology[J]. Hunan J Tradit Chin Med, 2021, 37( 11): 172- 177, 214. DOI: 10.16808/j.cnki.issn1003-7705.2021.11.057.

    朱荣火, 黄晶晶, 黄鸿娜, 等. 基于网络药理学探究大黄煎剂治疗轻微型肝性脑病的作用机制[J]. 湖南中医杂志, 2021, 37( 11): 172- 177, 214. DOI: 10.16808/j.cnki.issn1003-7705.2021.11.057.
    [8]
    ZHOU XX, ZENG SL, YAN HP, et al. Retention enema therapy with rhubarb decoction in the adjuvant treatment of hepatic encephalopathy[J]. J Guangxi Univ Chin Med, 2022, 25( 1): 12- 16. DOI: 10.3969/j.issn.2095-4441.2022.01.003.

    周学寻, 曾胜澜, 严惠萍, 等. 大黄煎剂保留灌肠辅助治疗肝性脑病的临床观察[J]. 广西中医药大学学报, 2022, 25( 1): 12- 16. DOI: 10.3969/j.issn.2095-4441.2022.01.003.
    [9]
    LUO S, KONG X, WU JR, et al. Neuroinflammation in acute hepatic encephalopathy rats: imaging and therapeutic effectiveness evaluation using 11C-PK11195 and 18F-DPA-714 micro-positron emission tomography[J]. Metab Brain Dis, 2018, 33( 5): 1733- 1742. DOI: 10.1007/s11011-018-0282-7.
    [10]
    WANG K, GUAN DS, ZHAO X, et al. Proteomics and metabolomics of raw rhubarb and wine-processed rhubarb in the treatment of rats with intracerebral hemorrhage[J]. Ann Transl Med, 2020, 8( 24): 1670. DOI: 10.21037/atm-20-7831.
    [11]
    ZHAO XL, ZHU SF, LI J, et al. Epigenetic changes in inflammatory genes and the protective effect of cooked rhubarb on pancreatic tissue of rats with chronic alcohol exposure[J]. Biomed Pharmacother, 2022, 146: 112587. DOI: 10.1016/j.biopha.2021.112587.
    [12]
    DONG LL, DU HL, ZHANG MY, et al. Anti-inflammatory effect of Rhein on ulcerative colitis via inhibiting PI3K/Akt/mTOR signaling pathway and regulating gut microbiota[J]. Phytother Res, 2022, 36( 5): 2081- 2094. DOI: 10.1002/ptr.7429.
    [13]
    ZHU D, XU JH, MO W. Effect of Luling Huoluo Granules on the inflammatory responses in rats with cervical spondylotic radiculopathy based on the PI3K/Akt signaling pathway[J]. J Changchun Univ Chin Med, 2022, 38( 5): 506- 509. DOI: 10.13463/j.cnki.cczyy.2022.05.010.

    朱栋, 许金海, 莫文. 基于PI3K/Akt信号通路探究鹿灵活络颗粒对神经根型颈椎病大鼠炎症反应的影响[J]. 长春中医药大学学报, 2022, 38( 5): 506- 509. DOI: 10.13463/j.cnki.cczyy.2022.05.010.
    [14]
    HUANG XJ, NI BW, MAO ZK, et al. NOV/CCN3 induces cartilage protection by inhibiting PI3K/AKT/mTOR pathway[J]. J Cell Mol Med, 2019, 23( 11): 7525- 7534. DOI: 10.1111/jcmm.14621.
    [15]
    LUO M, GUO JY, CAO WK. Inflammation: A novel target of current therapies for hepatic encephalopathy in liver cirrhosis[J]. World J Gastroenterol, 2015, 21( 41): 11815- 11824. DOI: 10.3748/wjg.v21.i41.11815.
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