Puerarin Inducing Angiogenesis And Its Molecular Mechanism

Objective: To investigate the effect and molecular mechanism of puerarin on angiogenesis.Methods: Using rat aortic ring assay and rat myocardial infarction model, the growth of microvessels was observed by counting the number of newly formed microvessels using microscope. Immunohistochemistry staining was used to examine myocardial microvessel density (MVD). Spectrophotometry was used to examine serum nitric oxide levels. The gene expression of myocardial HIF-1, VEGF and eNOS was examined by RT-PCR. Westem-Blot was applied to detect the protein expression of myocardial eNOS, iNOS, AKT, p-AKT.Results: (1) Puerarin was shown to have protective effect on myocardial ischemia. Puerarin (120, 60mg/kg, i.p.) could reduce the infarct area in the heart of rat with myocardium infarction. (2) Puerarin could induce angiogenesis. Puerarin at concentrations from 6.25 to 100mg/mL could induce angiogenesis in the culture of rat aortic rings. Puerarin (120mg/kg, i.p.) induced angiogenesis in ischemic and non-ischemic myocardium of rats with myocardial infarction. (3) The effect of puerarin on angiogenesis was realized through HIF-VEGF-AKT-eNOS-NO signal pathways shown below: a) Puerarin could increase the gene expression of myocardial HIF-1, VEGF and eNOS. b) Puerarin could increase myocardial eNOS protein expression and AKT protein phosphorylation level, c) Puerarin could increase serum nitric oxide level of rat with myocardium infarction.Conclusion: Puerarin induced angiogenesis in vitro and in vivo, which is one of the mechanisms of curing coronary artery diseases. The molecular mechanisms of puerarin on angiogenesis may be correlated with HIF-VEGF-AKT-eNOS-NO signal pathways.