Overexpression of glycogen synthase kinase 3beta in the treatment of myocardial infarction with cardiac stem cell transplantation / 中国组织工程研究

ABSTRACT

BACKGROUND:The mechanism and effect of glycogen synthase kinase 3β(GSK-3β) in the differentiation of cardiac stem cel s into cardiomyocytes are stil unclear, although GSK-3βis closely related to the life activities of cel s. OBJECTIVE:To investigate the changes of GSK-3βexpression in the treatment of myocardial infarction in rats undergoing cardiac stem cel transplantation. METHODS:The isolation and culture of cardiac stem cel s were performed in 10 neonatal rats. Lentivirus overexpressing GSK-3βor LacZ (control) was constructed and transferred into cardiac stem cel s. Animal model of myocardial infarction was made in 30 Sprague-Dawley rats. Six weeks after model preparation, rat models were assigned into GSK-3β, LacZ or PBS group. GSK-3βor LacZ overexpressing cardiac stem cel solution or PBS in equal volume was injected into the rat myocardium, respectively. Four weeks after transplantation, the cardiac function and myocardial col agen production in rats were detected and compared. RESULTS AND CONCLUSION:Compared with the other two groups, the left ventricular ejection fraction was significantly higher, and the left ventricular end diastolic diameter was significantly lower in the GSK-3βgroup (P<0.05). Hydroxyproline content, type I col agen mRNA, and type III col agen mRNA expression were significantly lower in the GSK-3βgroup than the other two groups (P<0.05). Findings from Masson staining showed that the content of blue-stained col agen was significantly lower in the GSK-3βgroup than the LacZ group. Moreover, lowest myocardial infarction size was found in the GSK-3βgroup (P<0.05). Al these experimental findings show that GSK-3 overexpression plays a positive role in promoting the therapeutic effect of cardiac stem cel transplantation.