Fluoxetine inhibited extracellular matrix of pulmonary artery and inflammation of lungs in monocrotaline-treated rats
查看参考文献37篇
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文摘
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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-β), 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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来源
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Acta Pharmacologica Sinica
,2011,32(2):217-222 【核心库】
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DOI
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10.1038/aps.2010.187
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关键词
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extracellular matrix
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inflammation
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pulmonary arterial hypertension
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selective serotonin reuptake inhibitor
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地址
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Department of Clinical Pharmacology, College of Pharmacy, China Medical University
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语种
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英文 |
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文献类型
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研究性论文 |
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ISSN
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1671-4083 |
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学科
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药学 |
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基金
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国家自然科学基金
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文献收藏号
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CSCD:4124334
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参考文献 共
37
共2页
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