Metformin enhanced the effect of pirfenidone on pulmonary fibrosis in mice

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal Pub Date : 2024-01-18 DOI:10.1111/crj.13731

Nana Liu, Yanqiu Song, Ting Liu, Hongyu Wang, Naihao Yu, Hui Ma

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Abstract

Background

The aim of the study is to observe the anti-inflammatory and antioxidative stress effects of metformin on bleomycin (BLM)-induced pulmonary fibrosis in mice.

Methods

Mice with BLM-induced pulmonary fibrosis were treated with pirfenidone, metformin, pirfenidone plus metformin and the NADPH oxidase 4 (NOX4) inhibitor diphenyleneiodonium chloride (DPI). Pathological changes and hydroxyproline (HPO) levels were examined in the lung tissue of mice with pulmonary fibrosis. Superoxide dismutase (SOD) activity and malonaldehyde (MDA) levels in lung tissue were determined.

Results

Compared with pirfenidone, pirfenidone plus metformin could reduce alveolar damage and collagen fibre deposition and alleviate BLM-induced pulmonary fibrosis. Lung HPO levels were significantly lower in the PFD + MET group than in the BLM group (p < 0.05). SOD levels in the lungs of mice were increased in the PFD + MET group than in the BLM group (p < 0.05). Metformin and pirfenidone plus metformin can reduce MDA levels (p < 0.05). Pirfenidone plus metformin could reduce HPO levels, increase SOD levels, and reduce MDA levels in the lungs of mice. There was a significant correlation between the HPO level and the Ashcroft score (r = 0.520, p < 0.001).

Conclusion

Metformin enhanced the antifibrotic effects of pirfenidone on BLM-treated mice. Moreover, these findings provide an experimental basis for examining whether metformin can improve the antifibrotic effects of pirfenidone on patients with idiopathic pulmonary fibrosis (IPF). It has broad therapeutic prospects for patients with IPF.

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二甲双胍增强了吡非尼酮对小鼠肺纤维化的作用

背景本研究旨在观察二甲双胍对博来霉素（BLM）诱导的小鼠肺纤维化的抗炎和抗氧化应激作用。方法用吡非尼酮、二甲双胍、吡非尼酮加二甲双胍和 NADPH 氧化酶 4（NOX4）抑制剂氯化二苯基碘（DPI）治疗博来霉素诱导的肺纤维化小鼠。对肺纤维化小鼠肺组织的病理变化和羟脯氨酸（HPO）水平进行了检测。测定了肺组织中的超氧化物歧化酶（SOD）活性和丙二醛（MDA）水平。结果与吡非尼酮相比，吡非尼酮加二甲双胍可减少肺泡损伤和胶原纤维沉积，减轻 BLM 诱导的肺纤维化。PFD + MET 组的肺 HPO 水平明显低于 BLM 组（p < 0.05）。与 BLM 组相比，PFD + MET 组小鼠肺中的 SOD 水平有所提高（p < 0.05）。二甲双胍和吡非尼酮加二甲双胍可降低 MDA 水平（p < 0.05）。吡非尼酮加二甲双胍可降低小鼠肺部的 HPO 水平，提高 SOD 水平，降低 MDA 水平。HPO 水平与 Ashcroft 评分之间存在明显的相关性（r = 0.520，p < 0.001）。结论二甲双胍增强了吡非尼酮对 BLM 治疗小鼠的抗纤维化作用。此外，这些发现为研究二甲双胍能否改善吡非尼酮对特发性肺纤维化（IPF）患者的抗纤维化作用提供了实验依据。它对 IPF 患者具有广阔的治疗前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Respiratory Journal 医学-呼吸系统

CiteScore

3.70

自引率

0.00%

发文量

104

审稿时长

>12 weeks

期刊介绍： Overview Effective with the 2016 volume, this journal will be published in an online-only format. Aims and Scope The Clinical Respiratory Journal (CRJ) provides a forum for clinical research in all areas of respiratory medicine from clinical lung disease to basic research relevant to the clinic. We publish original research, review articles, case studies, editorials and book reviews in all areas of clinical lung disease including: Asthma Allergy COPD Non-invasive ventilation Sleep related breathing disorders Interstitial lung diseases Lung cancer Clinical genetics Rhinitis Airway and lung infection Epidemiology Pediatrics CRJ provides a fast-track service for selected Phase II and Phase III trial studies. Keywords Clinical Respiratory Journal, respiratory, pulmonary, medicine, clinical, lung disease, Abstracting and Indexing Information Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Embase (Elsevier) Health & Medical Collection (ProQuest) Health Research Premium Collection (ProQuest) HEED: Health Economic Evaluations Database (Wiley-Blackwell) Hospital Premium Collection (ProQuest) Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) ProQuest Central (ProQuest) Science Citation Index Expanded (Clarivate Analytics) SCOPUS (Elsevier)