Original Article | Published:

Fluoxetine inhibited extracellular matrix of pulmonary artery and inflammation of lungs in monocrotaline-treated rats

Acta Pharmacologica Sinica volume 32, pages 217222 (2011) | Download Citation

Abstract

Aim:

To investigate the effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine on extracellular matrix (ECM) remodeling of the pulmonary artery and inflammation of the lungs in pulmonary arterial hypertension (PAH) induced by monocrotaline in rats.

Methods:

MCT-induced chronic PAH was established in Wistar rats. After treatment with fluoxetine for 3 weeks, pulmonary hemodynamic measurement and morphological investigation of lung tissues were undertaken. The main components of the ECM, elastin and collagen, were detected using Van Gieson stain and Orcein stain, respectively, or using Victoria-ponceau's double stain. The ECM proteolytic enzymes matrix metalloproteinase (MMP)-2 and MMP-9, and the tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2, were detected by Western blot. Inflammation of lung tissue was assayed using lung morphology and inflammatory cytokine expression.

Results:

Fluoxetine (2 and 10 mg/kg) significantly inhibited MCT-induced PAH, attenuated pulmonary arterial muscularization and ECM remodeling, and decreased MMP/TIMP expression. Fluoxetine also suppressed inflammatory responses in lung tissue and inhibited the expression of the inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein (MCP-1) and intercellular adhesion molecule-1 (ICAM-1).

Conclusion:

Fluoxetine inhibited MCT-induced ECM remodeling of the pulmonary artery and inflammation of lung tissue. These effects were related to its inhibition on MMPs/TIMPs and cytokine productions.

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Acknowledgements

Projects supported by National Natural Science Foundation of China (No 30973533 and No 30572194).

Author information

Affiliations

  1. Department of Clinical Pharmacology, College of Pharmacy, China Medical University, Shenyang 110001, China

    • Xue-qin Li
    • , Han-ming Wang
    • , Chun-guang Yang
    • , Xin-hua Zhang
    • , Dan-dan Han
    •  & Huai-liang Wang
  2. National Key Subject, Division of Respiratory Diseases, China Medical University, Shenyang 110001, China

    • Huai-liang Wang
  3. Department of Pharmacy, Zhongshan City People's Hospital, Zhongshan 528403, China

    • Xue-qin Li

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Correspondence to Huai-liang Wang.

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DOI

https://doi.org/10.1038/aps.2010.187

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