Study Of Protective Effects And Mechanism Of BFGF On Myocardial Ischemic/reperfusion Injury Of Rabbit Heart

Objective: To explore the protective effects of basic fibroblast growth factor (bFGF) on myocardial ischemic/reperfusion injury of rabbit heart and the their potential mechanism.Methods: The rabbit model of acute myocardial ischemic/ reperfusion was established by left descending anterior coronary artery (LAD) ligation for 40 min, followed by 180 min of reperfusion, myocardial infarct was determined by Electrocardiogram(ECG) EST. All this rabbits were divided into three groups: sham operated control group (sham), ischemic/reperfusion group (I/R), bFGF-treated group. bFGF-treated group was infused i.v.2 min before LAD occlusion and mid-reperfusion. The myocardial malondialdehyde (MDA) content, the superoxide dismutase (SOD) activity, the glutathione peroxidase (GSH-XP) activity, the reduced glutathione (GSH) content and the change of level of nitric oxide (NO) in plasm were observed. Cardiomyocyte apoptosis was determined by in situ TDT-mediated dUDP nick end labeling (TUNEL). The protein expression of Bcl-2 eNOS genes was studied by immunohistochemistry and the mean optical density(OD) values of the positive fields of protein expression were quantitatively examined by image analysis system.Results: Compared with I/R group, the concentration of NO was significantly increased in bFGF-treated group (p<0.01) , myocardial the SOD activity, the GSH-XP activity, and the GSH content were markedly increased and the MDA content was reduced in bFGF-treated group(p<0.01) . Cardiomyocyte apoptotic index was reduced and TUNEL positive nuclei were sparsely distributed and the number of positively stained nuclei was significantly reduced in bFGF-treated group (p<0.01) . The number of Bcl-2 protein positive cardiomyocytes was increased in bFGF-treated group (p<0.01) . The number of eNOS protein positive vascular endothelial cells was significantly increased in bFGF group(p<0.01) .Conclusion: This study suggests that bFGF may reduce the injury of peroxidation of myocardial cell membrane, expand blood vessel, increase blood flow and have antiapoptotic effect in cardiomyocytes. bFGF has protective effects on myocardial and vascular endothelial cells on ischemic/reperfusion injury. One of the mechanisms of the cardioprotective on I/R may be expansive blood vessel, increase blood flow associated with increase NO production and protective effects of myocardial cell and vascular endothelial cells. One of mechanisms of decreasing cardiomyocyte apoptosis may be associated with increase NO production by upregulated of eNOS gene expression in vascular endothelial cells and cardiomyocyte and upregulation of Bcl-2 gene expression in cardiomyocytes during I/R . bFGF have cardioprotective effects on myocardial ischemic/reperfusion injury and may have clinical applications in the treatment of ischemic heart disease.