Liangxue Jiedu Huayu Formula improves liver function of mice with acute-on-chronic liver failure by inhibiting excessive activation of the cGAS-STING signaling pathway.
10.12122/j.issn.1673-4254.2024.12.04
- Author:
Qiao TANG
1
;
Chao ZHOU
1
;
Zhaofang BAI
1
;
Qing YAO
1
;
Simin CHEN
1
;
Xinru WEN
1
;
Zhaoyun HE
1
;
Jin ZHANG
1
;
Ruisheng LI
1
;
Man GONG
1
Author Information
1. Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
- Publication Type:Journal Article
- Keywords:
Liangxue Jiedu Huayu Formula;
acute-on-chronic liver failure;
cGAS-STING signaling pathway;
interferon stimulating gene 15;
interferon‑β
- MeSH:
Animals;
Signal Transduction/drug effects*;
Mice;
Nucleotidyltransferases/metabolism*;
Mice, Inbred C57BL;
Acute-On-Chronic Liver Failure/etiology*;
Membrane Proteins/metabolism*;
Drugs, Chinese Herbal/therapeutic use*;
Liver/metabolism*;
Disease Models, Animal;
Interferon Regulatory Factor-3/metabolism*;
Interleukin-6/metabolism*;
Male
- From:
Journal of Southern Medical University
2024;44(12):2291-2299
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To explore the role of the cGAS-STING signaling pathway in the therapeutic mechanism of Liangxue Jiedu Huayu Formula (LXJDHYF) for acute-on-chronic liver failure (ACLF) in mice.
METHODS:Thirty C57BL/6 mice were randomly divided into blank control group, model group, low- and high-dose LXJDHYF groups, and H151 (a specific cGAS-STING pathway inhibitor) group (n=6). In all but the control group, the mice were treated with CCl4 to induce liver cirrhosis followed by intraperitoneal injections of lipopolysaccharide and D-amino galactose to establish mouse models of ACLF. After the treatments, the mouse livers were collected for HE and TUNEL staining, and serum levels of ALT, AST and TBil were determined. In bone marrow-derived macrophages (BMDMs) and liver tissues of ACLF mice, the expressions of cGAS-STING signaling pathway-related mRNAs including IFN‑β, ISG15, IL-6 and TNF-α were determined with RT-qPCR, and the phosphorylation levels of IRF3 and STING proteins were investigated using Western blotting.
RESULTS:Compared with the mice in the model group, the LXJDHYF-treated mice exhibited milder hepatocyte necrosis and inflammatory cell infiltration in the liver with significantly reduced hepatocyte apoptosis. LXJDHYF treatment also significantly lowered serum levels of ALT, AST, TBil, IL-6 and TNF-α in ACLF mice and effectively suppressed the expressions of cGAS-STING signaling pathway-related mRNA in both the BMDMs and the liver tissues and the phosphorylation of IRF3 and STING proteins in the BMDMs.
CONCLUSIONS:LXJDHYF can significantly improve liver function and attenuate inflammation in ACLF mice possibly by inhibiting excessive activation of the cGAS-STING signaling pathway.
