Benserazide Ameliorates Bleomycin-induced Pulmonary Fibrosis by Modulating the Hexokinase 2-mediated Glycolysis Pathway
10.3870/j.issn.1004-0781.2025.12.002
- VernacularTitle:苄丝肼调控己糖激酶2介导的糖酵解途径改善博来霉素诱导的肺纤维化
- Author:
Yurou HUANG
1
;
Meng ZHANG
;
Wenjing JIANG
;
Xiuxun WU
;
Liang CHEN
;
Yanjun DUAN
;
Yong WU
;
Zhenpeng QIU
Author Information
1. 湖北中医药大学药学院,武汉 430065
- Publication Type:Journal Article
- Keywords:
Benserazide;
Pulmonary fibrosis;
Glycolysis;
Hexokinase 2;
TGF-β/Smad2
- From:
Herald of Medicine
2025;44(12):1885-1893
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and mechanism of benserazide on bleomycin-induced pulmonary fibrosis in mice.Methods Male C57BL/6 mice were randomly divided into normal control group,model control group,pirfenidone group(50 mg·kg-1),and low-dose and high-dose benserazide groups(300 and 600 mg·kg-1),with 6 mice in each group.Except for normal control group,the other groups were given bleomycin(3.5 mg·kg-1)by non-invasive tracheal instillation to establish a mouse model of pulmonary fibrosis.Seven days after modeling,pirfenidone group and low-dose and high-dose benserazide groups were intragastrically administered the corresponding doses of drugs for 14 consecutive days.After the drug administration,the mice in each group were sacrificed.The pathological morphology of the lung tissue in each group was observed by hematoxylin-eosin(HE)staining and Masson staining.The content of hydroxyproline(HYP)in the lung tissue of mice,the content of lactic acid in the lung tissue and serum,and the activity of hexokinase(HK)in the lung tissue were detected by using kits.The expression levels of Collagen I and Fibronectin in the lung tissue of mice in each group were detected by immunohistochemistry.The expression levels of α-SMA,TGF-β1,Smad2,p-Smad2,TNF-α and IL-6 proteins in the lung tissue of mice in each group were detected by Western blotting.Results Compared with normal control group,the lung tissue structure of model control group mice was damaged,with thickened alveolar septa and fibrotic changes such as collagen accumulation.The content of HYP and lactic acid and the activity of HK in the lung tissue increased significantly,and the expression levels of Collagen I,Fibronectin,α-SMA,TGF-β1,Smad2,p-Smad2,TNF-α,and IL-6 proteins were significantly increased.Compared with model control group,treatment with benserazide significantly alleviated the pathological damage of lung tissue in mice,significantly reduced the content of HYP,lactic acid and HK activity in lung tissue,and significantly decreased the expression levels of Collagen I,Fibronectin,α-SMA,TGF-β1,Smad2,p-Smad2,TNF-α and IL-6 proteins.Conclusion Benserazide ameliorates bleomycin-induced pulmonary fibrosis in mice by modulating the HK2-mediated glycolysis pathway.
