ABSTRACT
AIM:To investigate the angiogenic effect and mechanisms of astragaloside IV(AS-IV)in rats with myocardial infarction via protein kinase D 1(PKD1)-histone deacetylase 5(HDAC5)-vascular endothelial growth factor (VEGF)signaling pathway.METHODS:The classic model of myocardial infarction by ligation of the left anterior de-scending coronary artery was replicated,and the rats were randomly divided into model group,AS-IV group,and AS-IV+CID755673(PKD1 inhibitor)group.The sham operation control group and DMSO control group were also set up.All the rats were given intravenous injection via caudal vein.The rats were sacrificed 4 weeks later,and segmental heart samples were used for HE staining and Masson staining.The expression of PKD1,HDAC5 and VEGF was analyzed by immunohis-tochemistry,RT-PCR and and Western blot.RESULTS:Compared with sham operation group and DMSO group,the myo-cardium in model group showed disordered arrangement, accompanied with necrotic myocardial cells and obvious fibrosis tissue.After treatment with AS-IV,the morphological changes of myocardium were obviously improved,and the number of new blood vessels increased significantly.However,after treatment with AS-IV+CID755673,the myocardial tissues of the rats became disordered again,with increased necrotic cells and some closed vessels.The mRNA and protein expression of PKD1,HDAC5 and VEGF in myocardial tissue in model group was significantly lower than that in sham operation and DMSO groups(P<0.05).The expression in AS-IV group was significantly higher than that in model group(P<0.01), while that in AS-IV+CID755673 group was significantly lower than that in AS-IV group(P<0.05).CONCLUSION:AS-IV promotes the angiogenesis of myocardial tissues in the rats after myocardial infarction partly by regulating the PKD 1-HDAC5-VEGF signaling pathway.