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BMC Pulmonary Medicine

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Open Access 01-12-2024 | Simvastatin | Research

Simvastatin attenuates silica-induced pulmonary inflammation and fibrosis in rats via the AMPK-NOX pathway

Authors: Cunxiang Bo, Fang Liu, Zewen Zhang, Zhongjun Du, Haidi Xiu, Zhenling Zhang, Ming Li, Caiqing Zhang, Qiang Jia

Published in: BMC Pulmonary Medicine | Issue 1/2024

Abstract

Background

Simvastatin (Sim), a hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in prevention and treatment of cardiovascular diseases. Studies have suggested that Sim exerts anti-fibrotic effects by interfering fibroblast proliferation and collagen synthesis. This study was to determine whether Sim could alleviate silica-induced pulmonary fibrosis and explore the underlying mechanisms.

Methods

The rat model of silicosis was established by the tracheal perfusion method and treated with Sim (5 or 10 mg/kg), AICAR (an AMPK agonist), and apocynin (a NOX inhibitor) for 28 days. Lung tissues were collected for further analyses including pathological histology, inflammatory response, oxidative stress, epithelial mesenchymal transformation (EMT), and the AMPK-NOX pathway.

Results

Sim significantly reduced silica-induced pulmonary inflammation and fibrosis at 28 days after administration. Sim could reduce the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α and transforming growth factor-β1 in lung tissues. The expressions of hydroxyproline, α-SMA and vimentin were down-regulated, while E-cad was increased in Sim-treated rats. In addition, NOX4, p22pox, p40phox, p-p47phox/p47phox expressions and ROS levels were all increased, whereas p-AMPK/AMPK was decreased in silica-induced rats. Sim or AICAR treatment could notably reverse the decrease of AMPK activity and increase of NOX activity induced by silica. Apocynin treatment exhibited similar protective effects to Sim, including down-regulating of oxidative stress and inhibition of the EMT process and inflammatory reactions.

Conclusions

Sim attenuates silica-induced pulmonary inflammation and fibrosis by downregulating EMT and oxidative stress through the AMPK-NOX pathway.

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Title: Simvastatin attenuates silica-induced pulmonary inflammation and fibrosis in rats via the AMPK-NOX pathway
Authors: Cunxiang Bo
Fang Liu
Zewen Zhang
Zhongjun Du
Haidi Xiu
Zhenling Zhang
Ming Li
Caiqing Zhang
Qiang Jia
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Simvastatin
Silicosis
Published in: BMC Pulmonary Medicine / Issue 1/2024
Electronic ISSN: 1471-2466
DOI: https://doi.org/10.1186/s12890-024-03014-9

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