The inflammatory role of TXA2 in heart after G-CSF and iron treatment

• Main Authors: Shu-hui Lin, 林淑惠
• Other Authors: Heng Lin
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/4hx6r5

碩士 === 慈濟大學 === 藥理暨毒理學研究所 === 96 === The purpose of this research was aimed at building up mice cardiac inflammation animal model by utilizing iron and G-CSF (I+G) injection. Meanwhile, the molecular pathogenesis of cardiac inflammation and possible treatment options will be studied by this animal model. Inducing cardiac inflammation by giving mice iron (I) and granulocyte-colony stimulating factor (G-CSF, G), this study displayed phagocytic infiltration in heart tissue, left ventricle thrombosis, and fibrosis. It postulates that during this inflammatory-dependent cardiac thrombosis, the inflammation would further aggravate under G-CSF induced leukocytosis. From the result of quantitative polymerase chain reaction, there was increased expression of intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractive protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-?? in I+G treated mice. Meanwhile, by immunohistochemical staining such as H&E, Masson’s trichrome and Prussian blue, it confirmed that there was large amount of iron deposition in heart tissue, and phagocyte and neutrophil infiltration. Consequently, this study verifies that the left ventricle thrombogenesis actually results from severe inflammation in heart. The inflammation of heart and intra-cardiac thrombosis had significant improvement after treating with simvastatin and in thromboxane A2 synthase (TXAS) knock out mice. The experiment outcome showed that simvastatin attenuated and inhibited intracardiac thrombogenesis by activating p-AKT/eNOS (phosphorylated Akt/endothelial nitric oxide synthase) pathway. Besides, compared with wild type mice being treated with I+G, the TXAS knock out mice had decreased level of TNF-?? reduced number of monocyte and neutrophil in blood, and diminished ICAM-1 and MCP-1 expression. What is more, by transfection NFAT (nuclear factor of activated T-cell) reporter plasmid into cardiac myofibroblast. From this experiment also showed TXA2 regulates the activity of NFAT to increase TNF-α expression by TXA2 receptor. Therefore, it can be concluded that the cardiac inflammation in I+G mouse model is caused by increased TNF-? level, which is stimulated by TXA2 regulated NFAT transcription activity.