中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 3
Mar.  2021
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(3): 642-647

Role and mechanism of hepatic stellate cells in the pathogenesis of mice with acute-on-chronic liver failure

DOI: 10.3969/j.issn.1001-5256.2021.03.027
  • a.

    Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China

  • b.

    Department of Ultrasound, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China

  • c.

    Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China

  • Received Date: 2020-08-19
  • Accepted Date: 2020-09-28
  • Published Date: 2021-03-20
    Abstract
  •   Objective  To investigate the role of hepatic stellate cell (HSC) inflammation in the pathogenesis of acute-on-chronic liver failure (ACLF).  Methods  A total of 45 male Kunming mice were randomly divided into control group, model group, and N-acetylcysteine (NAC) group. The mice in the model group and the NAC group were given injection of human serum albumin to establish a model of chronic liver disease, followed by intraperitoneal injection of the endotoxins lipopolysaccharide (LPS) and D-galactosamine (D-GlaN) to induce ACLF, and those in the control group were given injection of an equal volume of normal saline; the mice in the NAC group were given NAC since 1 week before the induction of NAC. The mice in the model group and the NAC group were sacrificed at 48 hours after the injection of LPS and D-GlaN. ELISA was used to measure the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in liver tissue; HE staining was used to determine liver pathological score; ELISA was used to measure the serum levels of LPS and interleukin-1β (IL-1β). LX2 cells were stimulated by LPS and H2O2 with the presence or absence of NAC, and ELISA was used to measure the levels of IL-1β and interleukin-6 (IL-6) in medium. LX2 cells were stimulated by LPS and H2O2, and then HL7702 cells were cultured with LX2 medium; Western blot was used to measure the expression of caspase-3 and caspase-8 in HL7702 cells, and flow cytometry was used to measure the apoptosis of HL7702 cells. A one-way analysis of variance was used for comparison of continuous data between multiple groups; the least significant difference t-test was used for comparison of data with homogeneity of variance between two groups, and the Tamhane's T2 test was used for comparison of data with heterogeneity of variance. The Kaplan-Meier survival analysis was used to evaluate survival time, and the log-rank test was used for comparison.  Results  At 48 hours, all mice in control group survived, while 3 mice in the model group and 8 mice in the NAC group survived, suggesting that the NAC group had a better survival rate of mice than the model group (P < 0.001). Compared with the control group and the NAC group, the model group had significant increases in the serum levels of AST and ALT and the level of MDA in liver tissue, as well as a significant reduction in the level of SOD in liver tissue (all P < 0.01). The model group had a significantly higher liver pathological score than the control group and the NAC group (both P < 0.05). Both LPS and H2O2 promoted the secretion of IL-1β and IL-6 in LX2 cells, and NAC effectively inhibited the pro-inflammatory effect of H2O2 and LPS (all P < 0.05). H2O2 and LPS acted on LX2 cells and promoted the apoptosis of HL7702 cells (all P < 0.05).  Conclusion  LPS can promote HSC inflammation via reactive oxygen species and participates in the progression of liver failure by inducing hepatocyte apoptosis.

     

    • FullText(HTML)
  • loading
    • References(16)
  • [1]
    Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Guideline for diagnosis and treatment of liver failure(2018)[J]. J Clin Hepatol, 2019, 35(1): 38-44. (in Chinese)

    中华医学会感染病学分会肝衰竭与人工肝学组, 中华医学会肝脏病学分会重型肝病与人工肝学组. 肝衰竭诊治指南(2018年版)[J]. 临床肝胆病杂志, 2019, 35(1): 38-44.
    [2]
    ZHANG J, ZHOU XM. Value of different scoring systems in predicting short-term mortality of patients with acute-on-chronic liver failure[J]. J Clin Hepatol, 2019, 35(9): 1990-1994. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2019.09.021

    张静, 周新民. 5种评分系统对慢加急性肝衰竭患者短期病死率的预测价值[J]. 临床肝胆病杂志, 2019, 35(9): 1990-1994. DOI: 10.3969/j.issn.1001-5256.2019.09.021
    [3]
    MEHTA G, MOOKERJEE RP, SHARMA V, et al. Systemic inflammation is associated with increased intrahepatic resistance and mortality in alcohol-related acute-on-chronic liver failure[J]. Liver Int, 2015, 35(3): 724-34. DOI: 10.1111/liv.12559
    [4]
    PAN C, GU Y, ZHANG W, et al. Dynamic changes of lipopolysaccharide levels in different phases of acute on chronic hepatitis B liver failure[J]. PLoS One, 2012, 7(11): e49460. DOI: 10.1371/journal.pone.0049460
    [5]
    FUJITA T, SOONTRAPA K, ITO Y, et al. Hepatic stellate cells relay inflammation signaling from sinusoids to parenchyma in mouse models of immune-mediated hepatitis[J]. Hepatology, 2016, 63(4): 1325-1339. DOI: 10.1002/hep.28112
    [6]
    LI J, ZHAO YR, TIAN Z. Roles of hepatic stellate cells in acute liver failure: From the perspective of inflammation and fibrosis[J]. World J Hepatol, 2019, 11(5): 412-420. DOI: 10.4254/wjh.v11.i5.412
    [7]
    JIN L, GAO H, WANG J, et al. Role and regulation of autophagy and apoptosis by nitric oxide in hepatic stellate cells during acute liver failure[J]. Liver Int, 2017, 37(11): 1651-1659. DOI: 10.1111/liv.13476
    [8]
    TIAN Z, CHEN Y, YAO N, et al. Role of mitophagy regulation by ROS in hepatic stellate cells during acute liver failure[J]. Am J Physiol Gastrointest Liver Physiol, 2018, 315(3): g374-g384. DOI: 10.1152/ajpgi.00032.2018
    [9]
    DAS J, GHOSH J, MANNA P, et al. Acetaminophen induced acute liver failure via oxidative stress and JNK activation: Protective role of taurine by the suppression of cytochrome P450 2E1[J]. Free Radic Res, 2010, 44(3): 340-55. DOI: 10.3109/10715760903513017
    [10]
    MONIAUX N, DARNAUD M, GARBIN K, et al. The reg3α (HIP/PAP) lectin suppresses extracellular oxidative stress in a murine model of acute liver failure[J]. PLoS One, 2015, 10(5): e0125584. DOI: 10.1371/journal.pone.0125584
    [11]
    KINUGASA H, WHELAN KA, TANAKA K, et al. Mitochondrial SOD2 regulates epithelial-mesenchymal transition and cell populations defined by differential CD44 expression[J]. Oncogene, 2015, 34(41): 5229-39. DOI: 10.1038/onc.2014.449
    [12]
    KIM SR, KIM DI, KIM SH, et al. NLRP3 inflammasome activation by mitochondrial ROS in bronchial epithelial cells is required for allergic inflammation[J]. Cell Death Dis, 2014, 5: e1498. DOI: 10.1038/cddis.2014.460
    [13]
    GAO YD, TIAN Y, ZHANG XY, et al. Effect of magnesium isoglycyrrhizinate on concanavalin A-induced acute liver failure in mice[J]. J Clin Hepatol, 2020, 36(7): 1571-1576. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2020.07.024

    高钰迪, 田原, 张向颖, 等. 异甘草酸镁对刀豆蛋白A诱导的急性肝衰竭小鼠模型的影响[J]. 临床肝胆病杂志, 2020, 36(7): 1571-1576. DOI: 10.3969/j.issn.1001-5256.2020.07.024
    [14]
    EDWARDS S, LALOR PF, NASH GB, et al. Lymphocyte traffic through sinusoidal endothelial cells is regulated by hepatocytes[J]. Hepatology, 2005, 41(3): 451-459. DOI: 10.1002/hep.20585
    [15]
    BIEGHS V, VERHEYEN F, van GORP PJ, et al. Internalization of modified lipids by CD36 and SR-A leads to hepatic inflammation and lysosomal cholesterol storage in Kupffer cells[J]. PLoS One, 2012, 7(3): e34378. DOI: 10.1371/journal.pone.0034378
    [16]
    DECHÂNE A, SOWA JP, GIESELER RK, et al. Acute liver failure is associated with elevated liver stiffness and hepatic stellate cell activation[J]. Hepatology, 2010, 52(3): 1008-1016. DOI: 10.1002/hep.23754
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(6)  / Tables(1)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (619) PDF downloads(50) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return