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

作　　者：Xue-qin LI Han-ming WANG Chun-guang YANG Xin-hua ZHANG Dan-dan HAN Huai-liang WANG 

机构地区：[1]Department of Clinical Pharmacology, College of Pharmacy [2]National Key Subject, Division of Respiratory Diseases, China Medical University, Shenyang 110001, China [3]Department of Pharmacy, Zhongshan City People's Hospital, Zhongshan 528403, China

出　　处：《Acta Pharmacologica Sinica》2011年第2期217-222,共6页中国药理学报（英文版）

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

摘　　要：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 metalioproteinase （TIMP）-I 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.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 metalioproteinase （TIMP）-I 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.

关 键 词：extracellular matrix INFLAMMATION pulmonary arterial hypertension selective serotonin reuptake inhibitor 

分 类 号：R[医药卫生]