Effect of metformin on liver fibrosis in a mouse model of Budd-Chiari syndrome

Jing YANG; Suxin LI; Yuehui ZHANG; Luhao LI; Zhaochen LIU; Dongqi SHEN; Xiaowei DANG

doi:10.3969/j.issn.1001-5256.2022.09.017

Volume 38 Issue 9

Sep. 2022

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Article Navigation > Journal of Clinical Hepatology > 2022 > 38(9): 2034-2039

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Effect of metformin on liver fibrosis in a mouse model of Budd-Chiari syndrome

DOI: 10.3969/j.issn.1001-5256.2022.09.017

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China

Research funding:

Henan Province Medical Science and Technology Research Plan Joint Provincial and Ministry Project (SB201901003)

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Corresponding author: DANG Xiaowei, dangxw1001@163.com(ORCID: 0000-0001-7940-6385)
Received Date: 2022-01-20
Accepted Date: 2022-03-02
Published Date: 2022-09-20

Abstract

Abstract

Objective To investigate the effect of metformin on liver fibrosis in a mouse model of Budd-Chiari syndrome and its mechanism. Methods A total of 30 male C57 mice were randomly divided into sham-operation group (SHAM group) with 6 mice, sham operation+ metformin group (SHAM+M group) with 5 mice, Budd-Chiari model group (BCS group) with 10 mice, and Budd-Chiari model+metformin group (BCS+M group) with 9 mice. The mice in the model group were treated with partial ligation of the inferior vena cava, those in the SHAM group were not treated with ligation, and those in the metformin group were given 0.1% metformin in drinking water besides modeling. The mice were sacrificed after 6 weeks. HE staining and picrosirius red staining were used to observe liver histopathology and collagen deposition; immunohistochemistry was used to measure the expressions of α-smooth muscle actin (α-SMA) and fibrinogen; quantitative real-time PCR was used to measure the mRNA expression of hypoxia-inducible factor 1α (HIF-1α) and type Ⅰ collagen (collagen 1), and Western blot was used to measure the relative protein expression levels of HIF-1α, vascular endothelial growth factor (VEGF), fibrinogen, α-SMA, and collagen 1. 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 Pathological staining showed that compared with the SHAM group, the BCS group had significant liver fibrosis, disordered arrangement of hepatocytes near the central vein, sinusoidal expansion with red blood cell deposition and a small amount of inflammatory cell infiltration, and collagen deposition. The BCS group had significant increases in the mRNA expression levels of HIF-1α and collagen 1 and the protein expression levels of α-SMA, collagen 1, HIF-1α, VEGF, and fibrinogen (all P < 0.05); compared with the BCS group, the BCS+M group had significant alleviation of liver fibrosis, red blood cell deposition, and collagen deposition and significant reductions in the mRNA expression levels of HIF-1α and collagen 1 and the protein expression levels of α-SMA, collagen 1, HIF-1α, VEGF, and fibrinogen (all P < 0.05). Conclusion Metformin can improve congestive liver fibrosis caused by Budd-Chiari syndrome, possibly by reducing microthrombus in hepatic sinusoid and inhibiting the HIF-1α/VEGF pathway.
- Budd-Chiari Syndrome,
- Liver Cirrhosis,
- Metformin,
- Mice, Inbred C57BL

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Effect of metformin on liver fibrosis in a mouse model of Budd-Chiari syndrome

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Effect of metformin on liver fibrosis in a mouse model of Budd-Chiari syndrome

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