Exogenous basic fibroblast growth factor promotes cardiac stem cell-mediated myocardial regeneration after miniswine acute myocardial infarction.

摘要

OBJECTIVE: To investigate the effects of exogenous basic fibroblast growth factor (bFGF) on myocardial regeneration after acute myocardial infarction (AMI). METHODS: AMI models were established by ligating the mid-third of left anterior descending artery, thereafter, miniswines were randomly divided into control (none treatment, n = 6) and bFGF groups (n = 6). For the bFGF group, bFGF (100 mug) was injected with a sterile microinjection at five sites within the ischemic region. 5-Bromo-2-deoxyuridine (250 mg) was administrated intravenously twice a week after the operation, to label cells undergoing DNA replication. The expression of stromal cell-derived factor-1alpha (SDF-1alpha) and CXC chemokine receptor 4 (CXCR4), cardiac stem cell-mediated myocardial regeneration, myocardial apoptosis, histological and immunohistochemical analyses, and cardiac function were evaluated at different time points. RESULTS: Four weeks after bFGF therapy, it showed an increased vessel density and myocardial perfusion (P < 0.001), upregulative expression of SDF-1alpha and CXCR4 (P < 0.001), increased c-kit and 5-bromo-2-deoxyuridine-positive cells (P < 0.001), enhanced myocardial viability (P < 0.001), and improved left ventricular ejection fraction (P = 0.007), compared with the control. CONCLUSION: Exogenous bFGF was shown to have increased angiogenesis and myocardial perfusion, promoted myocardial regeneration by activating the SDF-1alpha/CXCR4 axis, and thereby improved the cardiac function, which may provide a new therapeutic strategy for AMI.