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

Zhen TIAN; Lisha WANG; Naijuan YAO; Yingren ZHAO; Litao RUAN

doi:10.3969/j.issn.1001-5256.2021.03.027

Volume 37 Issue 3

Mar. 2021

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Article Navigation > Journal of Clinical Hepatology > 2021 > 37(3): 642-647

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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

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.
- Acute-On-Chronic Liver Failure,
- Hepatic Stellate Cells,
- Inflammation,
- Apoptosis

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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