Abstract: Objective The current study was designed to explore the effect of VEGF₁₆₅ gene combined with bFGF gene on neovascularization and infarct size of ischemic myocardium by intramyocardial injection.Methods 36 SD rats were divided randomly into five groups: control group(saline group,n=6);group A(pcDNA3.1 group,n=6);group B(VEGF group,n=8);group C(bFGF group,n=8);group D(combined VEGF with bFGF group,n=8).Then they received a ligation of the left anterior descending artery to induce myocardial infarction(MI).Saline,pcDNA3.1 vector,pcDNA3.1-VEGF₁₆₅,pcDNA3.1-bFGF,and VEGF combined with bFGF was intramyocardially injected at three seperated sites into the border zone of infarction.The hearts of rats were excised to evaluate the density of the capillary vessels and infarct size by HE staining and Masson's trichrome staining after four weeks.Immunohistochemical staining was used to evaluate protein expression of VEGF and bFGF. Results The density of myocardial capillary vessels in group B((37.4±)3.0/field),group C(34.0±2.9/field) and group D((41.9±)2.9/field) was significantly more than those in control(25.2±3.2/field) and group A(25.9±3.2/field)(P<0.01).The density of myocardial capillary vessels in group D was significantly more than those in group B and C(P<0.01).There was no significant difference in infarct size between group C(27.0±4.7)% and group D((25.1±)3.1)%,but the infarct sizes of these two groups were significantly decreased compared with those of group A(38.2±7.6)%,group B(34.9±4.2)% and control(37.6±6.2)%(P<0.01).Immunohistochemical staining for VEGF appeared to be positive staining in group B and group D,and immunohistochemical staining for bFGF appeared to be positive in in group C and group D.Conclusion The therapy of VEGF₁₆₅ combined with bFGF gene promotes angiogenesis significantly and reduces infarct size.The therapy effect of VEGF₁₆₅ combined with bFGF is better than only VEGF₁₆₅ gene or bFGF gene in improving angiogenesis,as well as better than only VEGF₁₆₅ gene in reducing infarct size.

Key words: vascular endothelial growth factor, basic fibroblast growth factor, gene therapy, myocardial infarction