Dissertation
Dissertation > Medicine, health > Pharmacy > Pharmacology > Experimental Pharmacology

Inhibition of Fenofibrate on Anglotensin Ⅱ-induced High Expresdon of Osteopontin in Cardiac Fibroblasts

Author LiWenJu
Tutor ZhengQiangZuo
School Fourth Military Medical University
Course Internal Medicine
Keywords Cardiac remodeling Myocardial fibrosis Angiotensin Ⅱ Cardiac fibroblasts Fenofibrate Osteopontin
CLC R965
Type Master's thesis
Year 2011
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Fenofibrate (fenofibrate) for general synthetic peroxisome proliferator-activated receptor α (peroxisome proliferator-activated receptorα, PPARα) agonist, clinical treatment of hypertriglyceridemia . Recent years non Norbert function gradually beyond the Lipid Metabolism attention, such as the number of studies show that it can regulation through a variety of ways such as hypertension or myocardial infarction, myocardial refactoring, is determined, it can play the role of anti-inflammatory and anti-fibrotic. Osteopontin (osteopontin, OPN), also called cytokine Eta-1 is a secreted glycoprotein phosphorylation by a variety of cells such as macrophages, neutrophils, dendritic cells, NK cells and the synthesis and secretion of T cells. Under normal circumstances, the mature heart only express low levels of OPN, but in a variety of pathological conditions significantly up-regulated the expression of OPN. OPN enhanced cardiac remodeling promote cardiac fibroblast growth and differentiation, promote collagen synthesis and reduces the expression and activity of MMP promote angiogenesis and cardiomyocyte hypertrophy and other role, to avoid the excessive enlargement of the ventricles, the maintenance of the heart The functional play a certain beneficial effect. Excessive cardiac structure changes also systolic and diastolic function of the heart, have a negative impact, in different stages of remodeling to regulate the expression of OPN may have a better prospect for clinical application. This study was to investigate whether fenofibrate on the simulated pathological conditions osteopontin expression in cardiac fibroblasts regulation, fenofibrate have a more comprehensive understanding of the role of the cardiovascular system. Objective: To investigate peroxidase enzyme proliferator-activated receptor α (PPARα) agonist fenofibrate elevated heart induced by angiotensin Ⅱ (Ang Ⅱ) into fibroblasts osteopontin expression. Methods: isolated and passaged culture SD neonatal rat cardiac fibroblasts, using different concentrations (0,25,50,100 μmol / L) fenofibrate Pretreatment After 1 hour, add the Ang Ⅱ 24 hours. Respectively, using real-time quantitative PCR and Western blot to detect the osteopontin mRNA and protein expression. Results: Fenofibrate significantly inhibited Ang II-induced cardiac fibroblasts osteopontin mRNA and protein expression, and a dose-dependent manner. Conclusion: Fenofibrate the heart into a significant inhibition of osteopontin expression in fibroblasts, which may play a part of the mechanism of the anti-fibrotic and anti-inflammatory effects in the cardiovascular system.

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