| Early growth response gene 1 (Egr-1), which encodes a zinc finger-containing transcription factor, is one of the immediate-early genes in response to stimulation, and its rapid up-regulation in mRNA, protein and nuclear binding activity has been demonstrated in the heart, lung, liver, gut and kidney after ischemia/reperfusion (I/R). With Egr-1-null mice or antisense Egr-1 oligodeoxyribonucleotide, previous studies have showed that Egr-1 might be a master switch in the pathogenesis of I/R injury due to its coordinating upregulation of divergent gene families underlying pathophysiological event of I/R.We have previously shown that N-n-butyl haloperidol iodide (F2) synthesized by our drug research lab reduces I/R-induced myocardial injury via blocking intracellular Ca2+ overload. However, we do not know whether these protective effects elicited by F2 are also related to a modulation of Egr-1 expression, a central and unifying role pathogenesis of myocardial I/R injury. In addition, myocardial tissue contains all different types of cells including cardiomyocytes, endothelial cells, vascular smooth muscle cells and inflammatory cells (i.e., neutrophils and macrophages), therefore, analysis from such a tissue block cannot differentiate the cell types that are responsible for action of F2. To resolve this issue, hypoxia/reoxygenation (H/R) model of cultured cardiomyocytes was served as the model of I/R in vitro for father study. The purpose of this study is to investigate the effects of F2 on Egr-1 mRNA transcription and protein expression in myocardial tissue and cultured cardiomycytes after I/R or H/R (I/R model in vitro), and research the relationship between the changes of Egr-1 and myocardial H/R injury, which is helpful to elucidate the new mechanisms, and discover target cells for action of F2.MethodsStudy in vivo: (1) The rat experimental models in vivo (M I/R) were established by 60 min left anterior descending coronary artery (LAD) occlusion followed by 180 min of...
|
PDF Full Text Request